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The emergence of biological agents and small molecule drugs has revolutionized the treatment landscape for psoriasis, yet there remains a lack of systematic reviews elucidating the efficacy and safety of drugs for patients with psoriasis and mental disorders (MDs). The aim was to systemically evaluate the efficacy and safety of FDA-approved psoriasis drugs on MD symptoms and MD drugs on psoriasis symptoms. We conducted comprehensive literature searches of the PubMed, Embase, and Cochrane Library from inception to March 24, 2024, identifying 116 relevant studies for inclusion. Our review encompasses 62 clinical trials and 54 case reports/series. Analyses of clinical trials revealed a positive impact of psoriasis drugs on MD, with notable exceptions including lithium and benzodiazepine receptor agonists, which exhibited adverse effects on psoriasis. Furthermore, analysis of case reports/series highlighted the efficacy of drugs such as apremilast, etanercept, infliximab, and secukinumab in ameliorating MD symptoms, contrasting with detrimental effects observed with methotrexate (MTX), cyclosporine, adalimumab, and secukinumab. Notably, tumor necrosis factor alpha (TNF-α) inhibitors and interleukin inhibitors demonstrated superior efficacy compared to conventional treatments. In the anxiety group, secukinumab showed the largest effective size as assessed by the Hospital Anxiety and Depression Scale - Anxiety (HADS-A) index; In the depression group, ixekizumab showed the largest effective size assessed by the 16-item Quick Inventory of Depressive Symptomology – Self-Report (QIDS-SR16) index. The extracted data cannot be meta-analyzed, as the measurement scale is not uniform. This systematic review provides robust evidence regarding treatment options for individuals with psoriasis and MD, emphasizing the potential benefits of specific drugs in managing both conditions concurrently. • In general, psoriasis drugs (conventional drugs, small molecule drugs, TNF-α inhibitors, IL inhibitors) all have a positive effect on MD. • TNF-α and IL inhibitors demonstrated superior efficacy compared to conventional treatments, particularly in patients with highly inflammatory conditions. • In the anxiety group, secukinumab showed the largest effective size as assessed by the HADS-A index; In the depression group, ixekizumab showed the largest effective size assessed by the QIDS-SR16 index. • MD drugs included gabapentin and paroxetine showed positive effect on psoriasis while lithium and BZRAs were reported to induce psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic inflammatory skin disease, is characterized by complex immune dysregulation and oxidative stress responses. The neonatal Fc receptor (FcRn) plays a crucial role in the development of autoimmune diseases. Analysis of clinical psoriasis samples demonstrated a negative correlation between FcRn expression in skin lesions and disease severity. However, the role of FcRn in this process remains unclear. This study aimed to investigate the involvement of FcRn in the pathogenesis and progression of psoriasis. In an imiquimod (IMQ)-induced psoriasis-like mouse model, FcRn expression was significantly decreased in the lesional skin, and transcriptome sequencing of the skin revealed activation of the ferroptosis pathway in psoriasis. This led to the hypothesis that FcRn could potentially regulate ferroptosis via the signal transducer and activating transcription factor 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) axis. Further experiments showed exacerbated psoriasis-like lesional skin and ferroptosis in FcRn-knockout mice, whereas intervention with the ferroptosis inhibitor Fer-1 or STAT3 inhibitor Stattic alleviated these symptoms. Critical binding sites for the transcription factor STAT3 were identified in the SLC7A11 promoter region at positions −1185 and −564 using the luciferase reporter assays and chromatin immunoprecipitation. The administration of 1,4-naphthoquinone (NQ), an FcRn agonist, effectively alleviated psoriasis-like skin lesions by inhibiting ferroptosis. This study highlights the molecular mechanisms of action of FcRn in psoriasis and provides an experimental basis for the development of novel therapeutic strategies targeting FcRn. [Display omitted] • Downregulation of FcRn may be a key factor in the pathogenesis of psoriasis. • FcRn regulates ferroptosis via the STAT3 signaling pathway in keratinocytes. • FcRn modulates psoriasis by regulating ferroptosis via the STAT3/SLC7A11 axis. • Critical STAT3 binding sites in SLC7A11 promoter identified for ferroptosis regulation. [ABSTRACT FROM AUTHOR]

Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings reveal a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model, adding to previous studies on cytokine levels using conventional immunochemical methods. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems. [Display omitted] • MMP landscape in skin inflammation mouse model analyzed for the first time using MS. • Increase in MMP-2, MMP-7, MMP-8 and MMP-13 abundance in inflamed mouse skin samples. • MMP-3, MMP-9, and MMP-10 were exclusively detected in inflamed mouse skin. • MMP profiles in inflamed mouse skin resemble those in skin of psoriasis patients. [ABSTRACT FROM AUTHOR]

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B 12 , possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B 12 @DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B 12 @DMAPs to downregulate the skin inflammatory environment. Overall, B 12 @DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare. [Display omitted] • Mechanical properties of PVP/PVA DMAPs are optimal to overcome the stratum corneum ex vivo. • B 12 @DMAPs success to create a drug permeation through the skin ex vivo. • B 12 @DMAPs components do not cause toxic effects in vitro in skin cell lines. • The inflammation triggered in vivo by oxazolone exposition is diminished by B 12 @DMAPs. • No histopathological damage is observed once B 12 @DMAPs are applied. • Myeloperoxidase activity and pro-inflammatory cytokine levels are normalised by B 12 @DMAPs. [ABSTRACT FROM AUTHOR]

Managing psoriasis (PsO) and its comorbidities, particularly psoriatic arthritis, often involves using interleukin (IL)-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. This study evaluates the risk of developing psoriatic arthritis in patients treated with IL-23 inhibitors compared to IL-12/23 inhibitors. This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with PsO. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of psoriatic arthritis (PsA), analyzed using a Cox regression hazard model and Kaplan-Meier estimates. The study included matched cohorts of patients treated with IL-23 inhibitors (n = 2273) and IL-12/23 inhibitors (n = 2995). Cox regression analysis revealed no significant difference in the cumulative incidence of PsA between the IL-23i and IL-12/23i cohorts (P =.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic PsO in both cohorts over the study period. Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. No significant difference but a numerically lower risk of psoriatic arthritis in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors was found, underscoring their comparable efficacy in PsO management and follow-up. [ABSTRACT FROM AUTHOR]

Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y 6 R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y 6 R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y 6 R and Th1 cells mediated by IL-27. Mechanistically, P2Y 6 R enhanced PLC β /p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y 6 R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y 6 R, exhibited remarkable anti-psoriasis effects targeting P2Y 6 R. Our study provides insights into the role of P2Y 6 R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y 6 R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic. Macrophage P2Y 6 R enhances release of IL-27 to mediate Th1 cell differentiation in the pathogenesis of psoriasis via PLC β /p-PKC/MAPK signaling, which could be reversed by a novel P2Y 6 R inhibitor FS-6. [Display omitted] [ABSTRACT FROM AUTHOR]

Connective tissue, rheumatological and dermatological conditions affect a large proportion of the pregnant population and have important implications for women and their babies. Some conditions are chronic but may occur de novo in pregnancy whereas some are seen only during pregnancy. Multidisciplinary care is essential to maximise fetal and maternal outcomes, since many of these women require immunosuppressive treatment and close monitoring of their pregnancies. The development of biological therapies has revolutionised treatment of many connective tissue and arthritic diseases, allowing both more targeted treatments and an increase in treatment options. Their impact on fertility is minimal compared to older treatments and hence more women are able to conceive. With new treatments there will always be concerns about safety in pregnancy but concerns around neonatal immunosuppression have largely been unfounded and the benefits of continuing medication are significant. This article uses four cases to illustrate the challenges of management. [ABSTRACT FROM AUTHOR]

Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [−15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of −0.6% (95% confidence interval; −3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. Data were only through week 28. SB17 was clinically biosimilar to UST up to week 28. [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic inflammatory skin disorder, is frequently linked with metabolic, cardiovascular, and psychological comorbidities. Recent research has highlighted the correlation between psoriasis and major depressive disorder (MDD); however, the underlying mechanism remains unclear. Commonly differentially expressed genes (DEGs) in psoriasis and MDD were identified and visualized using data from the GEO database. Subsequently, functional enrichment analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Genemania. The hub gene was selected through LASSO and Random Forest algorithms, validated in clinical tissues using Student's t -test and Receiver Operating Characteristic curve. To investigate the hub gene's function in disease phenotype, we established imiquimod (IMQ)-induced psoriasiform dermatitis and chronic unpredictable mild stress (CUMS) mouse models. Lentiviral shRNA interference was topically applied in mice, and downstream pathways were validated at the mRNA and protein levels. A total of 395 overlapping DEGs were identified from GSE121212 and GSE54568 datasets, and twenty core genes were extracted. Functional enrichment analysis revealed that the core genes were significantly associated with the Wnt signaling pathway, neurodegeneration, and energy metabolism. CD19 was identified as the hub gene through algorithms, and external validation showed remarkable AUC values of 0.69 and 0.74, respectively. The level of CD19 increased significantly in IMQ-treated and CUMS-treated mice. Suppression of CD19 significantly alleviated the phenotypes of IMQ-induced psoriasiform dermatitis and CUMS-induced depressive-like behaviors by regulating the PPARγ/β-catenin/Wnt3a pathway. CD19 may serve as a common biomarker or therapeutic target of psoriasis and MDD via PPARγ/β-catenin/Wnt3a pathway. • Identification of CD19 as a Shared Biomarker linking psoriasis and major depressive disorder. • CD19 could regulate the PPARγ/β-catenin/Wnt3a Pathway pathway. • CD19 could influence the pathogenesis of psoriasis and major depressive disorder. [ABSTRACT FROM AUTHOR]

The relationship between biologic treatments for psoriasis (PsO) and the development of inflammatory arthritis in patients is not fully understood. The objective of this study was to analyze the effects of biologic treatment on the development of inflammatory arthritis in patients with PsO. This retrospective study assessed patients with PsO identified in the Optum Clinformatics Data Mart database from Jan 2007 to Mar 2023 with no baseline diagnosis of inflammatory arthritis. Patients were stratified based on the class of initial biologic treatment (interleukin [IL] 23, IL-12/23, IL-17, or tumor necrosis factor [TNF] inhibitor) and followed for up to 3 years or development of inflammatory arthritis. Risk of developing inflammatory arthritis was assessed using a multivariate Cox proportional hazard model using IL-23 inhibitors as reference. Incidence rates of developing inflammatory arthritis expressed as events/100 person-years were 4.99, 7.29, 6.06, and 9.39 for IL-23, IL-17, IL-12/23, and TNF inhibitors, respectively. Adjusted hazard ratios were significantly higher for patients receiving IL-17 (1.44; P =.0294) and TNF (1.90; P <.0001) inhibitors when compared with patients receiving IL-23 inhibitors. Limitations include those associated with medical coding errors and the potential for protopathic bias. Patients receiving IL-23 inhibitors are at lower risk of developing inflammatory arthritis or psoriatic arthritis than those receiving IL-17 and TNF inhibitors. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is part of the psoriatic disease spectrum and is characterized by a chronic inflammatory process that affects entheses, tendons and joints. Cytokines produced by immune and non-immune cells play a central role in the pathogenesis of PsA by orchestrating key aspects of the inflammatory response. Pro-inflammatory cytokines such as TNF, IL-23 and IL-17 have been shown to regulate the initiation and progression of PsA, ultimately leading to the destruction of the architecture of the local tissues such as soft tissue, cartilage and bone. The important role of cytokines in PsA has been underscored by the clinical success of antibodies that neutralize their function. In addition to biologic agents targeting individual pro-inflammatory cytokines, signaling inhibitors that block multiple cytokines simultaneously such as JAK inhibitors have been approved for PsA therapy. In this review, we will focus on our current understanding of the role of cytokines in the disease process of PsA and discuss potential new treatment options based on modulation of cytokine function. [Display omitted] • Cytokines such as TNF and IL-23 play a crucial role in the pathogenesis of psoriatic arthritis. • Several preclinical studies indicate that inhibition of cytokine function by neutralizing antibodies can suppress disease activity. • Neutralizing antibodies targeting these cytokines have been approved for clinical therapy of psoriatic arthritis. • JAK inhibitors that target multiple cytokine signaling events simultaneously have been approved for therapy of psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs. To investigate the role of senescent CD4+ T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis. We explored the expression levels of p16INK4a and p21, classical markers of cellular senescence, in CD4+ T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis. Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16INK4a and p21 in CD4+ T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor (TCR) α and β chains, and expression of Tet methylcytosine dioxygenase 2 (Tet2) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4creTet2f/f mice was milder than that in Tet2f/f mice in the IMQ-induced psoriasis model. We revealed the roles of senescent CD4+ T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αβ repertoire, and regulation of the TET2-Th17 cell pathway. • We highlight the crucial role of senescent CD4+ T cells in pathogenesis of psoriasis. • The TET2 emerges as an important regulator of senescent CD4+ T cells in psoriasis. • Topical ABT-737 gel shows potential as a therapy for psoriasis by eliminating senescent cells. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease associated with lower quality of life and higher risk of anxiety and depression in adults. We investigate whether adolescents with psoriasis also experience poorer mental health than their peers. In this cross-sectional study, we included questionnaire data on psoriasis and mental health from the 18-year follow-up of the Danish National Birth Cohort. We estimated odds ratios (OR) and 95 % confidence intervals (CI) using a logistic regression with inverse probability weighting to account for potential selection bias, adjusted for potential confounders identified a priori. We estimated associations between self-reported psoriasis and multiple aspects of mental health (self-rated health, life satisfaction, mental well-being, loneliness, overall and internalizing behavioral difficulties, depressive symptoms, and anxiety symptoms). In sensitivity analyses, we examined doctor-diagnosed psoriasis and psoriasis with and without joint pain. Of the 44,838 included in this study, 1147 (2.6 %) reported psoriasis. Adolescents with psoriasis had a higher risk of nearly all outcomes, including depressive symptoms (OR 1.38; 1.19–1.58) and panic/agoraphobia among both males (OR 1.72; 1.33–2.19) and females (OR 1.60; 1.33–1.92). Associations attenuated when restricted to doctor-diagnosed psoriasis. Associations with poor mental health were mainly observed for adolescents with psoriasis also reporting joint pain. We could not establish temporality and lacked data on joint pain in referents. Psoriasis is associated with poor mental health in adolescents. This appears to be driven by adolescents with psoriasis also reporting joint pain and is less evident in those with a doctor-confirmed diagnosis. • Psoriasis is associated with poor mental health in adolescents. • Even milder forms of psoriasis can impact young people's mental health. • Joint pain has a negative impact on the mental health of adolescents with psoriasis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the prevalence of foot involvement in psoriatic arthritis and to describe its different clinical and radiological features. We conducted a cross sectional study including 40 patients with psoriatic arthritis over a period of 12 months. Anamnesis, clinical examination of feet, podoscopic examination, X-rays of feet and heels, and ultrasound in B mode and power Doppler mode were done for each patient. Foot involvement was found in 95% of cases. It was symptomatic in 70% and inaugural of the disease in 20% of cases. The hindfoot and the forefoot were the sites most affected (77.5% and 47.5% respectively). The involvement of the midfoot was rarer (25%). Dactylitis was found in 17.5% and deformities of forefoot were found in 22.5% of cases. Antalgic gait was noted in 17.5% and static disorders of foot at podoscopic examination were identified in 35% of cases. Feet dermatological manifestations were found in 45% of cases. Diagnosis of different rheumatological manifestations was based on clinical findings and caracteristic radiological images on X-rays. We demonstrate he sensitivity of ultrasound in the detection and the diagnosis of different foot lesions including enthesitis, synovitis and tenosynovitis, dactylitis, bone erosions and psoriatic nail dystrophy. [ABSTRACT FROM AUTHOR]

Patients with psoriasis are at increased risk of liver function abnormalities. Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus , and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo , CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. Cutibacterium acnes , which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune-mediated skin disease in which upper epidermal keratinocytes exhibit a senescent-like phenotype. In psoriatic skin, a variety of inflammatory cytokines can activate intracellular pathways including phosphatidylinositol 3-kinase (PI3K)/AKT signaling and RAS effectors. AKT and RAS participate to cellular senescence, but currently their role in senescence responses occurring in psoriasis have not yet been investigated. The role of AKT molecular axis and RAS activation was evaluated in the context of cellular senescence in psoriasis disease. RAS/AKT involvement in senescence was analyzed in psoriatic keratinocytes cultures subjected to multiple passages to promote senescence in vitro , as well as in skin lesions of patients affected by psoriasis. The impact of pharmacological inhibition of PI3K/AKT pathway on senescence and inflammation responses was tested in senescent psoriatic keratinocytes and in a psoriasiform dermatitis murine model induced by RAS overexpression in the upper epidermis of mice. We found AKT hyperactivation associated to the upregulation of senescence markers, in senescent psoriatic keratinocyte cultures, as well as in skin lesions of psoriatic patients. AKT-induced senescence was sustained by constitutive RAS activation, and down-stream responses were mediated by P53/P21 axis. PI3K/AKT inhibition contrasted senescence processes induced by cytokines in psoriatic keratinocytes. Additionally, RAS-induced psoriasis-like dermatitis in mice was accompanied by AKT upregulation, increase of senescence marker expression and by skin inflammation. In this model, both senescence and inflammation were significantly reduced by selective AKT inhibition. Therefore, targeting RAS-AKT pathway could be a promising novel strategy to counteract multiple psoriasis symptoms. • AKT is up-regulated in keratinocytes of psoriatic skin lesions in association to senescence markers over-expression. • AKT-induced senescence is sustained by constitutive RAS hyperactivation in keratinocytes cultures. • PI3K/AKT inhibition interferes with senescence responses induced by inflammatory cytokines in psoriatic keratinocytes. • RAS-induced psoriasiform murine model is accompanied by AKT upregulation, increase of senescence markers and skin inflammation. • Senescence processes and skin inflammation are reduced by AKT pharmacological inhibition in the psoriasiform murine model. [ABSTRACT FROM AUTHOR]

Scalp psoriasis is common and difficult to treat. To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. In this Phase 3b, randomized, double-blind, placebo (PBO)-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or PBO at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. Of patients treated with tildrakizumab (n = 89) vs PBO (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P <.00001). No serious treatment-related adverse events occurred. Only short-term data are presented. Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals. [ABSTRACT FROM AUTHOR]

Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 μg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was −2.6% and −4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. Posthoc analyses and low numbers. Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis. [ABSTRACT FROM AUTHOR]

A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined. To explore characteristics of fatigue and its potential drivers in a cohort of patients with psoriasis with or without PsA. Adults with psoriasis and a nonpsoriasis control group completed the Multidimensional Fatigue Inventory-20 questionnaire. Patients with psoriasis also reported joint pain intensity, pruritus, skin pain, and sleep problems using a numerical rating scale. Linear regression models were applied to continuous outcomes, and beta coefficients (β) for the slopes were estimated with 95% confidence intervals (CIs). Among 2741 adults with psoriasis (of which 593 also had PsA) and 3788 controls, the impact on total fatigue was greatest for PsA (β = 5.22; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25), compared with the general population (P trend <.0001). Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23 [95% CI, 2.03-2.44] for each 1-point increase in joint pain numerical rating scale score). We lacked information on the effect of pharmacotherapy. These findings highlight the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone. [ABSTRACT FROM AUTHOR]

Cardiovascular comorbidities are believed to cause higher mortality in psoriasis patients. Conversely, systemic therapy may improve overall survival. To evaluate the impact of different comorbidities and therapy on mortality risk of psoriasis patients in the entire population of Alberta, Canada (population 4.37 million). Cohorts of psoriasis cases (n = 18,618) and controls (ambulatory patients matched 1:3 by age and sex) were retrieved from Alberta Health Services Data Repository of Reporting database within the period 2012 to 2019. Cases were stratified according to Charlson Comorbidity Index, and the type of therapy. Mortality in psoriasis cohort was significantly higher than in the controls (median age of death 72.0 years vs 74.4 years, respectively). Charlson Comorbidity Index and comorbidities were strong predictors of mortality, in particular drug induced liver injury (hazard ratio 1.8, affective bipolar disease, hazard ratio 1.6, and major cardiovascular diseases. Mortality was lower in patients treated with biologics (hazard ratio 0.54). Some factors (psoriasis type and severity, response to treatment, smoking, alcohol intake) could not be measured. Hepatic injury, psychiatric affective disorders and cardiovascular disease were major determinants of overall survival in psoriasis. Biologic therapy was associated with a reduced mortality risk. [ABSTRACT FROM AUTHOR]

The routine use of targeted systemic immunomodulatory therapies has transformed outcomes for people with severe psoriasis, with skin clearance (clinical remission) rates up to 60% at 1 year of biologic treatment. However, psoriasis may recur following drug withdrawal, and as a result, patients tend to continue receiving costly treatment indefinitely. Here, we review research into the "inflammatory memory" in resolved psoriasis skin and the potential mechanisms leading to psoriasis recurrence following drug withdrawal. Research has implicated immune cells such as tissue resident memory T cells, Langerhans cells, and dermal dendritic cells, and there is growing interest in keratinocytes and fibroblasts. A better understanding of the interactions between these cell populations, enabled by single cell technologies, will help to elucidate the events underpinning the shift from remission to recurrence. This may inform the development of personalized strategies for sustaining remission while reducing long-term drug burden. [ABSTRACT FROM AUTHOR]

Various immune cells in the skin contribute to its function as a first line of defense against infection and disease, and the skin's dense innervation by pain-sensing sensory neurons protects the host against injury or damage signals. Dendritic cells (DCs) are a heterogeneous population of cells that link the innate immune response to the adaptive response by capturing, processing, and presenting antigens to promote T-cell differentiation and activation. DCs are abundant across peripheral tissues, including the skin, where they are found in the dermis and epidermis. Langerhans cells (LCs) are a DC subset located only in the epidermis; both populations of cells can migrate to lymph nodes to contribute to broad immune responses. Dermal DCs and LCs are found in close apposition with sensory nerve fibers in the skin and express neurotransmitter receptors, allowing them to communicate directly with the peripheral nervous system. Thus, neuroimmune signaling between DCs and/or LCs and sensory neurons can modulate physiologic and pathophysiologic pathways, including immune cell regulation, host defense, allergic response, homeostasis, and wound repair. Here, we summarize the latest discoveries on DC- and LC-neuron interaction with neurons while providing an overview of gaps and areas not previously explored. Understanding the interactions between these 2 defence systems may provide key insight into developing therapeutic targets for treating diseases such as psoriasis, neuropathic pain, and lupus. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that has wide-ranging roles, including regulation of inflammation and homeostasis. AhR is not a cell surface receptor; rather, it exists in a cytoplasmic complex that responds to a wide variety of structurally dissimilar endogenous, microbial, and environmental ligands. The ubiquitous expression of AhR, its ability to be activated by a wide range of ligands, and its capacity to act as a master regulator for gene expression and homeostasis make it a promising new therapeutic target. Clinical trials of tapinarof cream have now validated AhR agonism as a therapeutic approach that can deliver significant efficacy for treating inflammatory skin diseases, including psoriasis and atopic dermatitis. Tapinarof 1% cream is a first-in-class, nonsteroidal, topical, AhR agonist with a pharmacokinetic profile that results in localized exposure at sites of disease, avoiding systemic safety concerns, drug interactions, or off-target effects. Psoriasis and atopic dermatitis both involve epidermal inflammation, cellular immune responses, dysregulation of skin barrier protein expression, and oxidative stress. On the basis of the clinical effectiveness of tapinarof cream for treating inflammatory skin diseases, we review how targeting AhR may offer a significant opportunity in other conditions that share key aspects of pathogenesis, including asthma, inflammatory bowel disease, eosinophilic esophagitis, ophthalmic, and nervous system diseases. [ABSTRACT FROM AUTHOR]

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. This study shows that keratinocytes extracted from patients' psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic, immune-mediated disease, is a known risk factor for infectious complications following certain surgical procedures such as lower extremity arthroplasty. However, there is a paucity in the literature that observes the association of psoriasis and infectious complications following total shoulder arthroplasty (TSA). The primary research question was whether a diagnosis of psoriasis is associated with increased odds of short-term infectious complications and long-term surgical complications. A retrospective cohort analysis was performed using the PearlDiver all-payers' claims database. Patients who underwent primary TSA were identified using Current Procedural Terminology and International Classification of Diseases procedure codes. Patients were then stratified into two groups: (1) patients with psoriasis who underwent TSA, and (2) patients without psoriasis who underwent TSA. Primary outcomes included the incidence of 90-day infectious complications including periprosthetic joint infection, deep surgical site infection, and sepsis. Secondary outcomes included the incidence of 5-year surgical complications including all-cause revision, aseptic revision, and septic revision. Univariate and multivariable regression analyses were conducted to compare complications between the cohorts. In total, 89,321 patients were included in this study, with 3311 (3.71%) having psoriasis. Patients with psoriasis had significantly higher odds of 90-day infectious complications following TSA including periprosthetic joint infection (1.63; P =.014) and deep surgical site infection (1.79; P =.003), when compared to those without psoriasis. There were no significant differences in odds of 5-year all-cause revisions, septic revisions, and aseptic revisions between the two cohorts. Psoriasis is associated with significantly higher 90-day infectious complications but not long-term implant complications. Orthopedic surgeons should be aware of the increased acute infectious complications in this population, promote preoperative counseling and extensive infectious precautions, and consider the use of alternative prophylaxis against infection. These findings also have implications for risk adjustments in increasingly common bundled payments or shared risk payment models. [ABSTRACT FROM AUTHOR]

For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. Studies regarding infection rates after vaccination are lacking. Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases. [ABSTRACT FROM AUTHOR]

Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Sample size of subgroup analyses. Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor- α (TNF- α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF- α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF- α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF- α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF- α inhibitor, providing a promising lead compound for developing an antipsoriatic agent. Spirohypertones A and B, two new compounds with rearranged skeletons were isolated from Hypericum patulum and spirohypertone B was found to be a potential antipsoriatic via inhibit TNF- α. [Display omitted] [ABSTRACT FROM AUTHOR]

Mast cell degranulation plays a pivotal role in urticaria and is also an early histologic characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of interleukin (IL)-17A blockers remains unclear. To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathologic features were assessed. Patterns were compared between patients with ITAUR and nonurticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. Patients with ITAUR experienced early relapse compared with NUR group after treatment withdrawal. Transcriptomic and histopathologic analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A+ mast cells was inversely correlated with the duration of remission. The mechanism of mast cell activation in ITAUR has not been precisely elucidated. Ixekizumab treatment increases IL-17A+ mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal. [ABSTRACT FROM AUTHOR]

Keratinocyte dysdifferentiation and proinflammatory cytokine production play a central role in psoriatic inflammation. According to recent studies, the Rh family C glycoprotein (RHCG) enhances cell proliferation and disrupts cell differentiation. However, the specific role of RHCG psoriasis development remains unclear. We here explored the effect of RHCG on keratinocytes under psoriatic inflammation. The cell counting kit‑8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction. Both RHCG mRNA and protein levels increased in psoriatic skin. Notably, cultured keratinocytes treated with an M5 cocktail, which mimics psoriatic inflammation, exhibited higher RHCG expression. Furthermore, RHCG overexpression promoted keratinocyte proliferation, accompanied by an increase in the production of interleukin (IL)-1β, IL-6, and IL-8, and tumor necrosis factor-α. RHCG overexpression also resulted in higher expression of keratin 17, a differentiation marker. Conversely, RHCG gene knockdown reduced keratinocyte proliferation and cytokine secretion. RHCG inhibition in cells recovered both keratin 1 and loricrin expression. Additionally, RHCG overexpression facilitated the phosphorylation of nuclear factor-kappa B and extracellular signal-regulated protein kinase signaling pathways. Importantly, when these signaling pathways were inhibited, the effect of RHCG on keratinocytes was attenuated. These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment. • RHCG is upregulated in keratinocytes under psoriatic inflammation. • RHCG promotes the proliferation and cytokine secretion of keratinocytes. • RHCG contributes the dysdifferentiation of keratinocytes. • RHCG overexpression facilitates the phosphorylation of NF-κB and ERK proteins. [ABSTRACT FROM AUTHOR]

Scalp involvement in plaque psoriasis is challenging to treat. To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis. POETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16. Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P <.0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P <.0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population. Lack of data in milder scalp psoriasis. DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated. [ABSTRACT FROM AUTHOR]

Evolution has created complex mechanisms to sense environmental danger and protect tissues, with the nervous and immune systems playing pivotal roles. These systems work together, coordinating local and systemic reflexes to restore homeostasis in response to tissue injury and infection. By sharing receptors and ligands, they influence the pathogenesis of various diseases. Recently, a less-explored aspect of neuroimmune communication has emerged: the release of neuropeptides from immune cells and cytokines/chemokines from sensory neurons. This article reviews evidence of this unique neuroimmune interplay and its impact on the development of allergy, inflammation, itch, and pain. We highlight the effects of this neuroimmune signaling on vital processes such as host defense, tissue repair, and inflammation resolution, providing avenues for exploration of the underlying mechanisms and therapeutic potential of this signaling. [ABSTRACT FROM AUTHOR]