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Immunoglobulin E (IgE)‐mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity. While being the gold standard for diagnosis, oral food challenges are burdensome, and diagnostic tools based on specific IgE can be flawed. Furthering our understanding of the mechanisms behind food allergy onset, severity and persistence could help reveal immune profiles associated with the disease, to ultimately aid in diagnosis. Alterations to cytokine levels and immune cell ratios have been identified, though further research is needed to fully capture the heterogenous nature of food allergy. Moreover, the existence of such immune alterations also raises the question of potential wider systemic effects. For example, recent research has emphasised the existence and impact of neuro‐immune interactions and implicated behavioural and neurological changes associated with food allergy. This review will provide an overview of such food allergy‐driven neuro‐immune interactions, with the aim of emphasising the importance of furthering our understanding of the immune mechanisms underlying IgE‐mediated food allergy. [ABSTRACT FROM AUTHOR]

Breast implant surgery has evolved significantly, yet challenges such as capsular contracture remain a persistent concern. This review presents an in-depth analysis of recent advancements in understanding the immune mechanisms and clinical implications associated with silicone mammary implants (SMIs). The article systematically examines the complex interplay between immune responses and capsular fibrosis, emphasizing the pathophysiological mechanisms of inflammation in the etiology of this fibrotic response. It discusses innovations in biomaterial science, including the development of novel anti-biofilm coatings and immunomodulatory surfaces designed to enhance implant integration and minimize complications. Emphasis is placed on personalized risk assessment strategies, leveraging molecular insights to tailor interventions and improve patient outcomes. Emerging therapeutic targets, advancements in surgical techniques, and the refinement of post-operative care are also explored. Despite notable progress, challenges such as the variability in immune responses, the long-term efficacy of new interventions, and ethical considerations remain. Future research directions are identified, focusing on personalized medicine, advanced biomaterials, and bridging preclinical findings with clinical applications. As we advance from bench to bedside, this review illuminates the path forward, where interdisciplinary collaboration and continued inquiry weave together to enhance the art and science of breast implant surgery, transforming patient care into a realm of precision and excellence. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • MSC-Exos was extracted from pre-differentiated hBMSCs by ultracentrifugation. • MSC-Exos encapsulated hydrogel effectively promotes osteogenesis and angiogenesis. • The miR-18a-5p in MSC-Exos regulates macrophage polarization by the p53 pathway. Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as promising candidates for cell-free therapy in tissue regeneration. However, the native osteogenic and angiogenic capacities of MSC-Exos are often insufficient to repair critical-sized bone defects, and the underlying immune mechanisms remain elusive. Furthermore, achieving sustained delivery and stable activity of MSC-Exos at the defect site is essential for optimal therapeutic outcomes. Here, we extracted exosomes from osteogenically pre-differentiated human bone marrow mesenchymal stem cells (hBMSCs) by ultracentrifugation and encapsulated them in gelatin methacryloyl (GelMA) hydrogel to construct a composite scaffold. The resulting exosome-encapsulated hydrogel exhibited excellent mechanical properties and biocompatibility, facilitating sustained delivery of MSC-Exos. Osteogenic pre-differentiation significantly enhanced the osteogenic and angiogenic properties of MSC-Exos, promoting osteogenic differentiation of hBMSCs and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, MSC-Exos induced polarization of Raw264.7 cells from a pro-inflammatory phenotype to an anti-inflammatory phenotype under simulated inflammatory conditions, thereby creating an immune microenvironment conducive to osteogenesis. RNA sequencing and bioinformatics analysis revealed that MSC-Exos activate the p53 pathway through targeted delivery of internal microRNAs and regulate macrophage polarization by reducing DNA oxidative damage. Our study highlights the potential of osteogenic exosome-encapsulated composite hydrogels for the development of cell-free scaffolds in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Persistent human papillomavirus (HPV) infection is associated with the grading of cervical intraepithelial neoplasia (CIN), high-risk HPV infection, multiple HPV infections, high HPV load, HPV infection of surgical margin, and age in CIN after conization. The immune mechanism is complex and is primarily related to vaginal microecology disorders, immune escape, immune response impairment, and the release of regulatory cytokines. Currently, the treatment methods for postoperative persistent HPV infection include surgical treatment, antiviral treatment, vaccination, and other approaches. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy is a complex autoimmune disease with various underlying causes and significant clinical heterogeneity. There are large individual differences in its development, and the etiology and pathogenesis are still poorly understood. While it is known that immunobiological factors play a significant role in the pathophysiology of immunoglobulin A nephropathy, the specific nature of these factors has yet to be fully elucidated. Numerous investigations have verified that CD4+ and CD8+ T lymphocytes are involved in the immunopathogenesis of immunoglobulin A nephropathy. Furthermore, certain data also point to γδT cells' involvement in the pathophysiology of immunoglobulin A nephropathy. By thoroughly examining the mechanisms of action of these T cells in the context of immunoglobulin A nephropathy, this review sheds light on the immunopathogenesis of the disease and its associated factors. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF), a progressive lung disease characterized by irreversible lung dysfunction caused by fibroblast proliferation and excessive collagen deposition, is the result of persistent chronic inflammation of the lung parenchyma. Although the pathogenesis is not fully understood, the role of immune mechanisms such as innate immune response, adaptive immunity and immune regulation, and cytokines in the pathophysiological mechanism of pulmonary fibrosis have been gradually recognized. There are currently limited drugs available to treat IPF, and long-term use of these drugs may have many adverse effects. With the elucidation of the underlying immunological pathogenesis, the development of more valuable drugs targeting the immune system becomes possible. This review introduces the immunological pathogenesis of pulmonary fibrosis and the emerging drugs targeting the immune system in recent years, aiming to provide insights into the mechanism and treatment direction of pulmonary fibrosis.

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

Background: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. Methods: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab− CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. Results: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. Conclusion: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy. [ABSTRACT FROM AUTHOR]

Lupus Nephritis(LN) is the most common and severe visceral damage in systemic lupusery thematosus. Its physio pathological mechanism is complex, closely related to genetics, infection, sex hormones and immunity, among which the immune mechanism is one of the main mechanisms of LN. With the continuous exploration of the pathogenesis of LN. a number of biological agents that selectively intervene in specific targets have been developed and applied. In recent years, the vigorous development of traditional Chinese medicine has also provided new treatment options for further improving the prognosis of patients and reducing adverse effects. This article reviewed the immune mechanism and treatment progress of LN pathogenesis. so as to provide more reference for clinical diagnosis and treatment of LN. [ABSTRACT FROM AUTHOR]

Objective/backgroundSleep disturbance is a common problem in patients receiving chemotherapy. Purpose was to evaluate for perturbations in immune-inflammatory pathways between oncology patients with low versus very high levels of sleep disturbance.Patients/methodsSleep disturbance was evaluated using the General Sleep Disturbance Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct sleep disturbance profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 198) and microarray (n = 162) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between Low versus Very High sleep disturbance classes.ResultsIn the RNA sequencing and microarray samples, 59.1% and 51.9% of patients were in the Very High sleep disturbance class, respectively. Thirteen perturbed pathways were related to immune-inflammatory mechanisms (i.e., endocytosis, phagosome, antigen processing and presentation, natural killer cell mediated cytotoxicity, cytokine-cytokine receptor interaction, apoptosis, neutrophil extracellular trap formation, nucleotide-binding and oligomerization domain-like receptor signaling, Th17 cell differentiation, intestinal immune network for immunoglobulin A production, T-cell receptor signaling, complement and coagulation cascades, and tumor necrosis factor signaling).ConclusionsFirst study to identify perturbations in immune-inflammatory pathways associated with very high levels of sleep disturbance in oncology outpatients. Findings suggest that complex immune-inflammatory interactions underlie sleep disturbance.

Simple Summary: This commentary focuses on experimental techniques used by researchers to understand how the immune system of an animal can acclimate, or change, to function across different body temperatures. I categorized studies as using three different, broad techniques: (1) allowing animal body temperatures to change naturally; (2) manipulating body temperatures of live animals in a controlled environment; and (3) manipulating temperatures of immune components (plasma, cells, etc.) in laboratory assays. I reviewed how the current literature used these techniques, with the conclusion that combinations of the three different techniques increased a mechanistic understanding of acclimation. In particular, cell-based techniques seem under-utilized and can lead to a greater understanding of how an animal may be changing the numbers of cells in their bodies or changing the cells themselves to function across different temperatures. This short review focuses on current experimental designs to quantify immune acclimation in animals. Especially in the face of rapidly changing thermal regimes, thermal acclimation of immune function has the potential to impact host–pathogen relationships and the fitness of hosts. While much of the field of ecoimmunology has focused on vertebrates and insects, broad interest in how animals can acclimate to temperatures spans taxa. The literature shows a recent increase in thermal acclimation studies in the past six years. I categorized studies as focusing on (1) natural thermal variation in the environment (e.g., seasonal), (2) in vivo manipulation of animals in captive conditions, and (3) in vitro assays using biological samples taken from wild or captive animals. I detail the strengths and weaknesses of these approaches, with an emphasis on mechanisms of acclimation at different levels of organization (organismal and cellular). These two mechanisms are not mutually exclusive, and a greater combination of the three techniques listed above will increase our knowledge of the diversity of mechanisms used by animals to acclimate to changing thermal regimes. Finally, I suggest that functional assays of immune system cells (such as quantification of phagocytosis) are an accessible and non-taxa-specific way to tease apart the effects of animals upregulating quantities of immune effectors (cells) and changes in the function of immune effectors (cellular performance) due to structural changes in cells such as those of membranes and enzymes. [ABSTRACT FROM AUTHOR]

Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in‐depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in‐depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.

Lung cancer has the highestmortality rate among all cancers worldwide. The 5-year overall survival rate for non-small cell lung cancer (NSCLC) is estimated at around 26%, whereas for small cell lung cancer (SCLC), the survival rate is only approximately 7%. This disease places a significant financial and psychological burden on individuals worldwide. The symbiotic microbiota in the human body has been significantly associated with the occurrence, progression, and prognosis of various diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Studies have demonstrated that respiratory symbiotic microorganisms and their metabolites play a crucial role in modulating immune function and contributing to the pathophysiology of lung cancer through their interactions with the host. In this review, we provide a comprehensive overview of the microbial characteristics associated with lung cancer, with a focus on the respiratory tract microbiota from different locations, including saliva, sputum, bronchoalveolar lavage fluid (BALF), bronchial brush samples, and tissue. We describe the respiratory tract microbiota's biodiversity characteristics by anatomical region, elucidating distinct pathological features, staging, metastasis, host chromosomal mutations, immune therapies, and the differentiated symbiotic microbiota under the influence of environmental factors. Our exploration investigates the intrinsic mechanisms linking the microbiota and its host. Furthermore, we have also provided a comprehensive review of the immune mechanisms by whichmicrobiota are implicated in the development of lung cancer. Dysbiosis of the respiratory microbiota can promote or inhibit tumor progression through various mechanisms, including DNA damage and genomic instability, activation and regulation of the innate and adaptive immune systems, and stimulation of epithelial cells leading to the upregulation of carcinogenesisrelated pathways. [ABSTRACT FROM AUTHOR]

Single‐cell transcriptomics analysis is an advanced technology that can describe the intracellular transcriptome in complex tissues. It profiles and analyses datasets by single‐cell RNA sequencing. Neurodegenerative diseases are identified by the abnormal apoptosis of neurons in the brain with few or no effective therapy strategies at present, which has been a growing healthcare concern and brought a great burden to society. The transcriptome of individual cells provides deep insights into previously unforeseen cellular heterogeneity and gene expression differences in neurodegenerative disorders. It detects multiple cell subsets and functional changes during pathological progression, which deepens the understanding of the molecular underpinnings and cellular basis of neurodegenerative diseases. Furthermore, the transcriptome analysis of immune cells shows the regulation of immune response. Different subtypes of immune cells and their interaction are found to contribute to disease progression. This finding enables the discovery of novel targets and biomarkers for early diagnosis. In this review, we emphasize the principles of the technology, and its recent progress in the study of cellular heterogeneity and immune mechanisms in neurodegenerative diseases. The application of single‐cell transcriptomics analysis in neurodegenerative disorders would help explore the pathogenesis of these diseases and develop novel therapeutic methods. [ABSTRACT FROM AUTHOR]

The worldwide rising prevalence of food allergy is a major public health concern. Standard care consists of allergen avoidance and rescue medication upon accidental exposure. Oral immunotherapy (OIT) is increasingly being studied as a treatment option. Although desensitization (an increased reaction threshold) is often achieved during OIT, sustained unresponsiveness (SU; clinical nonreactivity after finishing OIT) is not achieved in most patients. A few studies have investigated the effectiveness of OIT in children younger than 4 years of age (early = e‐OIT) and have shown a much more favorable outcome in terms of SU development. Together with food allergy prevention studies, which have demonstrated high efficacy of early oral allergen exposure, the outcomes of e‐OIT studies indicate an early‐life window of opportunity to achieve SU, allowing unrestricted dietary intake. However, the underlying mechanism of the high effectiveness of e‐OIT is not understood yet. Both cohort and OIT studies indicate early‐life immune plasticity. An immature food‐allergic response in the first years of life seems to be a major driver of this immune plasticity, along with a higher tolerogenic immunological state. Allergy maturation can likely be disrupted effectively by early intervention, preventing the development of persistent food allergy. Upcoming studies will provide important additional data on the safety, feasibility, and effectiveness of e‐OIT. Combined with immune mechanistic studies, this should inform the implementation of e‐OIT. [ABSTRACT FROM AUTHOR]

During development of the spontaneously hypertensive rat (SHR), several distinct but closely related lines were generated. Most lines are resistant to hypertensive renal disease. However, the SHR-A3 line (stroke-prone SHR) experiences end-organ injury (EOI) and provides a model of injury susceptibility that can be used to uncover genetic causation. In the present study, we generated a congenic line in which three distinct disease loci in SHR-A3 are concurrently replaced with homologous loci from an injury-resistant SHR line (SHR-B2). Verification that all three loci were homozygously replaced in this triple congenic line [SHR-A3(Trip B2)] while the genetic background of SHR-A3 was fully retained was obtained by whole genome sequencing. Congenic genome substitution was without effect on systolic blood pressure [198.9 ± 3.34 mmHg, mean ± SE, SHR-A3(Trip B2) = 194.7 ± 2.55 mmHg]. Measures of renal injury (albuminuria, histological injury scores, and urinary biomarker levels) were reduced in SHR-A3(Trip B2) animals, even though only 4.5 Mbases of the 2.8 Gbases of the SHR-B2 genome (0.16% of the genome) was transferred into the congenic line. The gene content of the three congenic loci and the functional effects of gene polymorphism within suggest a role of immunoglobulin in EOI pathogenesis. To prove the role of antibodies in EOI in SHR-A3, we generated an SHR-A3 line in which expression from the immunoglobulin heavy chain gene was knocked out (SHR-A3-IGHKO). Animals in the SHR-A3-IGHKO line lack B cells and immunoglobulin, but the hypertensive phenotype is not affected. Renal injury, however, was reduced in this line, confirming a pathogenic role for immunoglobulin in hypertensive EOI in this model of heritable risk. NEW & NOTEWORTHY Here, we used a polygenic animal model of hypertensive renal disease to show that genetic variation affecting antibody formation underlies hypertensive renal disease. We proved the genetic thesis by generating an immunoglobulin knockout in the susceptible animal model. [ABSTRACT FROM AUTHOR]

During the first waves of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one of the front-line protections against viral infections, and the immune responses of the nasal mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: the infection of sustentacular cells and the inflammatory reaction of the nasal epithelium. The former triggers OD and the latter likely prolongs OD. These two alternative mechanisms may act in parallel; the infection of sustentacular cells is more important for OD occurrence because sustentacular cells are more likely to be the entry point of SARS-CoV-2 than olfactory neurons and more susceptible to early injury. Furthermore, sustentacular cells abundantly express transmembrane protease, serine 2 (TMPRSS2) and play a major role in the olfactory epithelium. OD occurrence in COVID-19 has revealed crucial roles of sustentacular cells. This review aims to elucidate how immune responses of the nasal epithelium contribute to COVID-19-related OD. Understanding the underlying immune mechanisms of the nasal epithelium in OD may aid in the development of improved medical treatments for COVID-19-related OD. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI)‐based cancer therapies cause a variety of cutaneous immune‐related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP‐irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. Methods: BP‐irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T‐cells (CD3 and CD8), T helper 1 (TH1) cells (Tbet), TH2 cells (Gata3), TH17 cells (RORγT), and regulatory T‐cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. Results: Compared with de novo BP controls, BP‐irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll‐like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH2, TH17, and B‐cell immune response. BP‐irAE demonstrated a greater density of Tbet+ (TH1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. Conclusions: BP‐irAE exhibited activation of the TLR4/complement‐driven classical innate immune response pathway, with dermal TH1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP‐irAE. [ABSTRACT FROM AUTHOR]

Peanut oral immunotherapy (pOIT) is the only FDA-approved treatment for food allergy and its adoption amongst allergist immunologists and their patients is growing. pOIT is the subject of numerous clinical trials, however, the focus is often on treatment efficacy, safety, and tolerability, rather than identifying patients most likely to benefit from pOIT. Here, we review existing data on the clinical and immunological outcomes of pOIT that inform best practices for pOIT candidate selection. In this review, we describe the natural history of peanut allergy, summarize immunological and clinical outcomes of pOIT at different ages, discuss the optimization of pOIT in key age groups, and finally suggest an ideal age range at which to initiate pOIT for best outcomes. pOIT is currently underutilized by patients and allergist-immunologists. Developing guidelines for selecting appropriate patients and optimizing treatment may help to increase access to pOIT. Many aspects of pOIT need additional study to further our understanding of the optimal timing to start pOIT, with careful consideration to clinical, immunological, and quality of life outcomes. [ABSTRACT FROM AUTHOR]

Abstract Tubercular association with serpiginous choroiditis, also called ‘serpiginous-like choroiditis’ or ‘multifocal serpiginoid choroiditis’ (MSC) is reported from world over, especially from endemic countries. Though the exact mechanism is not yet clear, a direct or indirect infectious trigger by Mycobacterium tuberculosis (MTB) is believed to cause choroiditis. The link of immune mechanisms with ocular inflammation caused by MTB is emerging, and has been supported by both experimental and human data. The molecular and histopathological findings of tubercular serpiginous-like choroiditis have been demonstrated in clinicopathological reports, as well as in animal models. Young to middle-aged healthy males are more frequently affected. The choroiditis lesions of tubercular serpiginous-like choroiditis evolve as multifocal lesions, affecting the retinal periphery as well as posterior pole. They begin as discrete lesions, and spread in a serpiginoid pattern to become confluent. Fundus imaging including autofluorescence is extremely helpful in monitoring patients for response to therapy. Its diagnosis is essentially clinical. Corroborative evidence is obtained by a positive tuberculin skin test, or a positive QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia) test, and/or radiological (chest X-ray or chest CT scan) evidence of TB elsewhere in the body. Systemic corticosteroids are the mainstay of therapy to control active inflammation, while ATT helps to reduce recurrence of inflammatory attacks. Immunosuppressive agents are indicated in cases with relentless progression, paradoxical worsening, or recurrent choroiditis.

The blood-retinal barrier (BRB) is a well-recognized mechanism that underlies the retina’s immunological privilege. The BRB is formed locally by inhibitory molecules that bind to cell membranes, as well as by the suppression of systemic immune responses. Recent studies have revealed that microglial cells are essential for maintaining immunological privilege within the retina by regulating the immune response. They achieve this by enhancing or reducing ocular inflammation. Furthermore, retinal pigment epithelium (RPE) regulates the behavior of immune cells within the retina, which can lead microglial cells to reduce inflammation and promote immunological tolerance. With the aim of better understanding the biology of immunological processes within the retina, this article reviews the BRB and discusses the factors, systemic immune responses, microglia, RPE, and their associated enzymes that enable the BRB.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to the classes Bacilli and Clostridia in the phylum Firmicutes, have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa (primarily in the class Clostridia) and show that their presence correlates with impaired differentiation of IL-10-secreting, regulatory T lymphocytes in vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of proinflammatory, IFN-γ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control-derived spore-forming bacteria were able to induce similar IL-10-expressing Treg immunoregulatory responses, thus ameliorating symptoms of experimental allergic encephalomyelitis (EAE). Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro.

Introduction: Obesity is a risk factor for asthma morbidity, associated with less responsiveness to inhaled corticosteroids. CD4+ T-cells are central to the immunology of asthma and may contribute to the unique obese asthma phenotype. We sought to characterize the single cell CD4+ Transcriptional profile differences in obese children with asthma compared to normal weight children with asthma. Methods: Eight normal weight and obese participants with asthma were clinically phenotyped and matched based on asthma control. Peripheral blood (PB) CD4+ T-cells were sorted, and single cell RNA sequencing was conducted. Cell clusters were identified by canonical gene expression, differential gene expression and reactome pathway analysis was applied. The obese PB bulk transcriptomic signature from the U-BIOPRED pediatric cohort was assessed in our cohort as well. Results: Obese children with asthma have a distinct CD4+ transcriptional profile with differential gene expression. There were more activated protein tyrosine phosphate receptor type C (PTPRC) high cells and less PTPRC low in the obese children. Obese children had higher enrichment of the neutrophil degranulation, interleukin-7 (IL-7) receptor and IL-7-related janus kinase-signal transducer and activator of transcription signaling pathways. Genes previously associated with more severe asthma, IL-32, FKBP5 gene expression, IL-6 and Rho transcriptional signaling, were also enriched in obese children with asthma. Discussion: Our findings shed insight into the molecular mechanisms underpinning more severe and steroid-resistant asthma among obese children. Further investigation is needed to identify potential new therapeutic targets for this group.

Rationale and Objectives: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most severe complications of systemic lupus erythematosus (SLE), and its early biomarkers and immune mechanisms remain unclear. This study utilizes Resting-State functional magnetic resonance imaging (rs-fMRI) to explore early neuroimaging biomarkers and potential immune mechanisms of brain injury in SLE, with a particular focus on anti-ribosomal P protein antibody (ARPA)., Materials and Methods: A total of 47 SLE patients and 33 healthy controls (HCs) underwent rs-fMRI. Amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) values were compared between SLE and HC groups, and between ARPA-positive and ARPA-negative SLE patients. Correlation analyses were conducted to evaluate relationships between neuroimaging indicators and clinical indicators, including immunoglobulins and antiphospholipid antibodies. Conventional MRI findings, including white matter hyperintensities (WMHs), were also assessed., Results: SLE patients exhibited significant ALFF and DC alterations in regions associated with cognitive and sensory functions, including the inferior frontal and occipital regions. Notably, ARPA-positive SLE patients showed increased ALFF and DC values in areas related to cognitive and emotional regulation. Additionally, ACA-IgM and IgG correlate with brain injury in ARPA-positive patients. WMHs were more prevalent in ARPA-positive patients, with age and IgG levels identified as predictive markers for WMHs., Conclusion: The combined use of ALFF and DC can effectively identify early biomarkers of brain injury in SLE patients. ARPA may synergize with other immune factors to combine to impair some brain functions, offering new insights into the immune-mediated mechanisms of SLE-related brain injury and potential targets for therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

ABSTRACT Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung. IMPORTANCE Aspergillus fumigatus is a fungal pathogen that causes serious and often fatal disease in humans. The surface of Aspergillus is composed of complex sugar molecules. Recognition of these carbohydrates by immune cells by carbohydrate lectin receptors can lead to clearance of the infection or, in some cases, benefit the fungus by dampening the host response. Galactomannan is a carbohydrate that is part of the cell surface of Aspergillus but is also released during infection and is found in patient lungs as well as their bloodstreams. The significance of our research is that we have identified Dectin-2 as a mammalian immune cell receptor that recognizes, binds, and signals in response to galactomannan. These results enhance our understanding of how this carbohydrate interacts with the immune system at the site of infection and will lead to broader understanding of how release of galactomannan by Aspergillus effects the immune response in infected patients.

Tubercular association with serpiginous choroiditis, also called 'serpiginous-like choroiditis' or 'multifocal serpiginoid choroiditis' (MSC) is reported from world over, especially from endemic countries. Though the exact mechanism is not yet clear, a direct or indirect infectious trigger by Mycobacterium tuberculosis (MTB) is believed to cause choroiditis. The link of immune mechanisms with ocular inflammation caused by MTB is emerging, and has been supported by both experimental and human data. The molecular and histopathological findings of tubercular serpiginous-like choroiditis have been demonstrated in clinicopathological reports, as well as in animal models. Young to middle-aged healthy males are more frequently affected. The choroiditis lesions of tubercular serpiginous-like choroiditis evolve as multifocal lesions, affecting the retinal periphery as well as posterior pole. They begin as discrete lesions, and spread in a serpiginoid pattern to become confluent. Fundus imaging including autofluorescence is extremely helpful in monitoring patients for response to therapy. Its diagnosis is essentially clinical. Corroborative evidence is obtained by a positive tuberculin skin test, or a positive QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia) test, and/or radiological (chest X-ray or chest CT scan) evidence of TB elsewhere in the body. Systemic corticosteroids are the mainstay of therapy to control active inflammation, while ATT helps to reduce recurrence of inflammatory attacks. Immunosuppressive agents are indicated in cases with relentless progression, paradoxical worsening, or recurrent choroiditis. [ABSTRACT FROM AUTHOR]

Management of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining symptomatic after failing biological and/or targeted synthetic DMARDs. Multiple factors can contribute to D2T RA, including treatment non-adherence, comorbidities and co-existing mimicking diseases (e.g. fibromyalgia). Additionally, currently available biological and/or targeted synthetic DMARDs may be truly ineffective ('true' refractory RA) and/or lead to unacceptable side effects. In this narrative review based on a systematic literature search, an overview of underlying (immune) mechanisms is presented. Potential scenarios are discussed including the influence of different levels of gene expression and clinical characteristics. Although the exact underlying mechanisms remain largely unknown, the heterogeneity between individual patients supports the assumption that D2T RA is a syndrome involving different pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Due to underlying allograft rejection and renal ischemia reperfusion injury (IRI) inducing renal injury, hyperuricemia (HUA) is one of the common complications after renal transplantation and may be a major contributor to reduced renal function. Currently, there are no uniform mechanisms of HUA after renal transplantation. This review aimed to figure out the immune mechanisms of HUA after renal transplantation and the molecular mechanisms of HUA-induced renal injury to provide new insights into renal function protection and prolonged survival time of grafts. MATERIALS AND METHODS: The search terms included 'Hyperuricemia', 'Renal transplantation', 'Urea acid', 'Gout' 'Graft Rejection', 'Graft Survival'. Databases including PubMed, Cochrane Library, Embase, Clinicaltrials.gov and China National Knowledge Infrastructure (CNKI) were searched for studies including mechanisms of hyperuricemia after renal transplantation from the beginning of databases to March 2022. RESULTS: Our study reviews the immune mechanisms of HUA after renal transplantation. HUA induces renal injury mainly by renal inflammation, oxidative stress, and endothelial dysfunction. IRI contributes to increased inflammation in renal grafts, mediates the recruitment of various inflammatory cell types. CONCLUSIONS: Due to underlying allograft rejection and IRI, renal transplant recipients are especially prone to HUA. HUA further reduces renal function and even graft loss. Treg targeting could be a novel therapeutic approach in renal transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT Capsular polysaccharides (CPSs) are important antigenic targets against bacterial infections. As T-independent antigens, however, CPSs elicit short-lived immune responses in adults and are poorly immunogenic in young children. Coupling CPS with protein carriers enhances anti-CPS responses and generates long-lasting immune memory. However, the mechanisms whereby carrier proteins accomplish this are not fully understood. Here, we dissect different mechanisms whereby carrier proteins enhance anti-CPS immunity. We show how coupling CPS with protein carriers modifies the interaction of CPS with antigen-presenting cells, enables a dual-activation mechanism for CPS-specific B cells via interaction with CPS- or carrier-specific T helper cells, and potentiates the recall of anti-CPS responses by engaging memory T helper cells during subsequent vaccination or bacterial exposure. Our findings provide new insights into the immunological basis of carrier-mediated anti-CPS immunity and may help in the design of more effective CPS-based vaccines. IMPORTANCE Polysaccharide capsules, the outermost shells of many bacterial pathogens, play a role in pathogenesis and protect bacteria against the immune system. Generating antipolysaccharide antibodies by vaccination has provided effective protection against infectious diseases caused by encapsulated bacteria. However, most pure polysaccharide preparations are poorly immunogenic, particularly in young children. To circumvent this problem, vaccines have been developed using polysaccharides associated with protein carriers. The precise mechanism whereby protein carriers enhance the immunogenicity of the polysaccharide remains unclear. The significance of our research is in elucidating the different roles played by carriers in facilitating polysaccharide processing and presentation, priming polysaccharide-specific B cells, and potentiating recall antipolysaccharide responses. Overall, our work provides new insights into the immunological basis of carrier-mediated antipolysaccharide immunity and may help in the design of more effective polysaccharide-based vaccines.

Women terminating HRT often were able to subsequently stop asthma treatment.[10] 17 -estradiol was higher in post-menopausal women with severe asthma when compared to mild-to-moderate asthma, assessed both in serum and in induced sputum.[11] On the contrary, it has been demonstrated that premenopausal asthma in women is characterized by low estradiol concentrations and persistent neutrophilic airway inflammation, characteristic of the non-T2 asthma phenotype. Keywords: asthma; estrogen; immune mechanisms; menopause; testosterone EN asthma estrogen immune mechanisms menopause testosterone 620 622 3 03/08/23 20230301 NES 230301 Asthma affects people of all ages and frequently persists throughout the whole life span. [Extracted from the article]

Berberine hydrochloride is the main active ingredient of Coptis chinensis, which has demonstrated significant antibacterial activity against bacteria. However, the molecular mechanism underlying its effects is unclear in crabs. In this study, we used transcriptome sequencing to investigate the molecules involved in the therapeutic and defensive responses of Charybdis japonica infected with 105 colony-forming units (CFU)/L of Aeromonas hydrophila following treatment with berberine hydrochloride. A total of 5,409 differentially expressed genes were observed after exposure of C. japonicus for 72 h to 100 mg/L berberine hydrochloride, 100 mg/L berberine hydrochloride plus injection of 105 CFU/L A. hydrophila, and a control group injected with equal amount of physiological saline solution. Enrichment analysis revealed that these genes were involved in metabolism, cellular processes, signal transduction, and immune function. The transcriptomic results indicated that exposure to berberine hydrochloride activated glutathione metabolism, oxidative phosphorylation, fatty acid degradation, retinol metabolism, pyruvate metabolism, and the hypoxia-inducible factor 1 signaling pathway. Transcriptomic analysis and relative mRNA level analysis also identified acid hydrolase genes and phagosomal genes as key factors regulating the adaptation of acid berberine-infused C. japonicus to infection with A. hydrophila, Based on the ability of berberine hydrochloride to induce acid hydrolase and phagosomal gene expression, which can in turn remove bacteria, immersion in berberine hydrochloride may remove A. hydrophila and thus improve the survival of C. japonica. The results of this study provided a new scientific basis for the potential role of berberine hydrochloride in the immune mechanisms of crabs.

Cytotoxic CD4 T lymphocytes (CD4-CTL) are important in antiviral immunity. For example, we have previously shown that in mice, CD4-CTL are important to control ectromelia virus (ECTV) infection. How viral infections induce CD4-CTL responses remains incompletely understood. We demonstrate here that not only ECTV but also vaccinia virus and lymphocytic choriomeningitis virus induce CD4-CTL, though the response to ECTV is stronger. Using ECTV, we also demonstrate that in contrast to CD8- CTL, CD4-CTL differentiation requires constant virus replication and ceases once the virus is controlled. We also show that major histocompatibility complex class II molecules on CD11c1 cells are required for CD4-CTL differentiation and for mousepox resistance. Transcriptional analysis indicated that antiviral CD4-CTL and noncytolytic T helper 1 (Th1) CD4 T cells have similar transcriptional profiles, suggesting that CD4-CTL are terminally differentiated classical Th1 cells. Interestingly, CD4-CTL and classical Th1 cells expressed similar mRNA levels of the transcription factors ThPOK and GATA-3, necessary for CD4 T cell linage commitment, and Runx3, required for CD8 T cell development and effector function. However, at the protein level, CD4-CTL had higher levels of the three transcription factors, suggesting that further posttranscriptional regulation is required for CD4-CTL differentiation. Finally, CRISPR/Cas9-mediated deletion of Runx3 in CD4 T cells inhibited CD4-CTL but not classical Th1 cell differentiation in response to ECTV infection. These results further our understanding of the mechanisms of CD4-CTL differentiation during viral infection and the role of posttranscriptionally regulated Runx3 in this process. [ABSTRACT FROM AUTHOR]

Abstract Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.

The problem of studying cardiovascular diseases (CVD) for a long time remains extremely important, and, therefore, there are many works that offer new ways to diagnose and treat this group of diseases. Great opportunities are provided by the study of molecular interactions for a more accurate understanding of the pathogenesis of cardiovascular pathology. Many studies have recently been devoted to finding potential markers of CVD risk with the aim of more accurate and early diagnosis. In this review we analyze the latest literature data dedicated to the role of heat shock protein 70 (HSP70) in cardiovascular pathology. HSP70 take part in such processes as arterial hypertension, coronary heart disease, and atherosclerosis. In atherogenesis, serum heat shock proteins 70 play a major role. It has been proven that in patients with a high concentration of heat shock protein molecules circulating in the blood, increased values of the carotid intima-media complex were observed. The important role of antibodies to circulating HSP70 is noted. Found an association of high levels of these antibodies with atherosclerosis in patients with arterial hypertension in history, with myocardial infarction. Low levels of anti-HSP70 antibodies are observed in patients with acute coronary syndrome. This proves the complexity of the mechanism and the dual role of antibodies against serum heat shock proteins 70. Thus, antibodies against heat shock proteins 70 can be assessed as a protective marker, and as a predictor, which requires further study, and the HSP70 molecules themselves can somehow to participate in the development of cardiovascular pathologies. Much attention is paid to the role of the inflammatory process and the mechanisms of innate immunity in CVD. As it is currently believed that Danger-associated molecular patterns (DAMPs) are involved in the pathogenesis of these pathologies in the context of a “hazard/damage” model. According to this model, the triggering factor is stress, leading to the release of DAMPs and their binding to innate immunity receptors - Toll-like receptors (TLRs). Activation of TLRs triggers the signaling cascade in the cell leading to the synthesis of pro-inflammatory cytokines. This contributes to the development of inflammation, which can provoke the emergence of new pathological processes in the body and worsen the course of existing diseases. The identification of new potential markers and knowledge of the molecular mechanisms of the pathogenesis of CVD can play an important role in the development of a new individual approach to the prevention of cardiovascular diseases.

The neuropathology of hippocampal seizure foci in human temporal lobe epilepsy (TLE) and several animal models of epilepsy reveal extensive neuronal loss along with astrocyte and microglial activation. Studies of these models have advanced hypotheses that propose both pathological changes are essential for seizure generation. However, some seizure foci in human TLE show an extreme loss of neurons in all hippocampal fields, giving weight to hypotheses that favor neuroglia as major players. The epileptic (EL) mouse is a seizure model in which there is no observable neuron loss but associated proliferation of microglia and astrocytes and provides a good model to study the role of activated neuroglia in the presence of an apparently normal population of neurons. While many studies have been carried out on the EL mouse, there is a paucity of studies on the molecular changes in the EL mouse hippocampus, which may provide insight on the role of neuroglia in epileptogenesis. In this paper we have applied high throughput gene expression analysis to identify the molecular changes in the hippocampus that may explain the pathological processes. We have observed several classes of genes whose expression levels are changed. It is hypothesized that the upregulation of heat shock proteins (HSP70, HSP72, FOSL2 (HSP40), and their molecular chaperones BAG3 and DNAJB5 along with the down regulated gene MALAT1 may contribute to the neuroprotection observed. The increased expression of BDNF along with immediate early gene expression (FosB, JunB, ERG4, NR4A1, NR4A2, FBXO3) and the down regulation of GABRD, DBP and MALAT1 it is hypothesized may contribute to the hyperexcitability of the hippocampal neurons in this model. Activated astrocytes and microglia may also contribute to excitability pathomechanisms. Activated astrocytes in the ELS mouse are deficient in glutamine synthetase and thus reduce the clearance of extracellular glutamate. Activated microglia which may be associated with C1Q and MHC class I molecules we propose may mediate a process of selective removal of defective GABAergic synapses through a process akin to trogocytosis that may reduce neuronal inhibition and favor hyperexcitability.

Adjuvants are included in vaccine formulations to enhance the immunogenicity and efficacy of vaccines. MF59® is an oil-in-water emulsion adjuvant and licensed for use in pandemic and seasonal influenza vaccines in many countries. MF59 is safe and well tolerated in humans. MF59-adjuvanted vaccination spares vaccine dose and enhances hemagglutination inhibiting antibodies against homologous and heterologous influenza virus strains. The mechanisms of MF59 involve rapid induction of chemokines, inflammatory cytokines, recruiting multiple immune cells, uric acid and benign apoptosis of certain innate immune cells. The adjuvant effects of MF59 on generating vaccine-specific isotype-switched IgG antibodies, effector CD8 T cells, and protective immunity were retained even in a CD4-deficient condition by inducing effective immune-competent microenvironment with various innate and antigen presenting cells in a mouse model. CD4-independent adjuvant effects of MF59 might contribute to improving the vaccine efficacy in children, the elderly, and immunocompromised patients as well as in healthy adults. Further studies will be needed to broaden the use of MF59 in various vaccine antigens and populations as well as lead to better understanding of the action mechanisms of MF59 adjuvant.

ANCA‐associated vasculitis (AAV) is a group of chronic inflammatory diseases of small‐ and medium‐sized vessels, which are broadly subdivided based on organ manifestations and disease‐specific autoantibodies. The so called anti‐neutrophil cytoplasmic antibodies (ANCA) mostly target one of the enzymes, proteinase 3 (PR3) or myeloperoxidase (MPO). Accumulating genetic data demonstrates that these two autoantibodies discriminate two distinct disease entities, more so than the clinical subdivision which is mainly criteria‐based. Treatment of AAV includes heavy immunosuppression and is guided by which organs that are involved. Generally, patients with PR3‐ANCA display higher risk for disease relapse than patients with MPO‐ANCA. In this review, we will focus on the autoimmune features of PR3+ AAV and our current understanding of its triggers and the potential translation into clinical practice. [ABSTRACT FROM AUTHOR]

In general, it is rare for an endocrine physician to be at the fore-front of any pandemic, as most of the acutely ill patients are managed by first responders and emergency physicians. With increasing evidence that patients having endocrine and metabolic disorders, especially uncontrolled, are the ones expected to have poorer outcomes during the ongoing coronavirus disease 2019 (COVID-19) pandemic, it has brought the endocrine physician to the fore-front of management. Several publications have reported the endocrine and metabolic conditions that may be considered risk factors for acquiring the new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) infection, but the direct evidence whether SARS-CoV-2 may directly lead to endocrinopathies causing disorders that make the prognosis of affected patients worse, are lacking. Most of the endocrine disorders, but their etiopathogenesis or treatment thereof alter the way the body's immune defense mechanisms are triggered. Furthermore, in specific scenarios, ongoing treatment may have to be discontinued/modified. There is still paucity of data to alter the already available "best practices or clinical recommendations" statements. In the absence of any specific recommendations, it is the left to the judgment of the treating endocrine physician to adapt the available recommendations/guidelines on the basis of the clinical judgment. [ABSTRACT FROM AUTHOR]

An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4+ T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8+ T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4+ and CD8+ T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4+ T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4+ T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8+T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.

Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Biomarkers of vaccine induced protective immunity are elusive in humans, while a cautionary message on the translatability of data obtained from current animal models has emanated from vaccine research and development efforts against other important human pathogens. In this commentary, we highlight recent advances in Chlamydia vaccine development and discuss their implications in the context of a rational approach to the design of a human C. trachomatis vaccine.

We aimed to comprehensively understand the functional mechanisms of immunity, especially of the CD8+/− subsets of gamma delta (γδ) T cells, using an RNA-sequencing analysis. Herein, γδ T cells were obtained from bronchial lymph node tissues of 38-day-old (after weaning 10-day: D10) and 56-day-old (after weaning 28-day: D28) weaned pigs and sorted into CD8+ and CD8− groups. Differentially expressed genes (DEGs) were identified based on the CD8 groups at D10 and D28 time points. We confirmed 1699 DEGs between D10 CD8+ versus D10 CD8− groups and 1784 DEGs between D28 CD8+ versus D28 CD8− groups; 646 upregulated and 561 downregulated DEGs were common. The common upregulated DEGs were enriched in the cytokine–cytokine receptor interaction and T cell receptor (TCR) signaling pathway, and the common downregulated DEGs were enriched in the B cell receptor signaling pathway. Further, chemokine-related genes, interferon gamma, and CD40 ligand were involved in the cytokine–cytokine receptor interaction and TCR signaling pathway, which are associated with inter-regulation in immunity. We expect our results to form the basic data required for understanding the mechanisms of γδ T cells in pigs; however, further studies are required in order to reveal the dynamic changes in γδ T cells under pathogenic infections, such as those by viruses.

Hymenoptera venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after Hymenoptera venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure long-term tolerance post-therapy.