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Lung epithelial cells play a protective role in the respiratory system. However, various pathological factors such as infection, trauma, and inflammation can lead to damage to lung epithelial cells, causing lung diseases. T cells play a key role in lung epithelial cells damage and repair, and participate in these processes by contacting with respiratory epithelial cells or releasing of various cytokines. Different subpopulations of T cells are responsible for enhancing anti-inflammatory responses, clearing infections, and promoting angiogenesis and epithelial cell proliferation. This review aims to summarize the role of T cells in lung epithelial cell damage and repair, as well as the mechanisms involved in the development and remission of lung diseases.

Non‐small cell lung cancer (NSCLC) is the leading cause of cancer‐related mortality, with tumour heterogeneity, fueled by cancer stem cells (CSCs), intricately linked to treatment resistance. Therefore, it is imperative to advance therapeutic strategies targeting CSCs in NSCLC. In this study, we utilized RNA sequencing to investigate metabolic pathway alterations in NSCLC CSCs and identified a crucial role of nitric oxide (NO) metabolism in governing CSC stemness, primarily through modulation of the Notch1 protein. Mechanistically, NO‐induced S‐nitrosylation of Notch1 facilitated its interaction with the deubiquitylase UCHL1, leading to increased Notch1 protein stability and enhanced CSC stemness. By inhibiting NO synthesis and downregulating UCHL1 expression, we validated the impact of NO on the Notch signalling pathway and CSC stemness. Importantly, targeting NO effectively reduced CSC populations within patient‐derived organoids (PDOs) during radiotherapy. This mechanism presents a promising therapeutic target to surmount radiotherapy resistance in NSCLC treatment. [ABSTRACT FROM AUTHOR]

This article explores the role of mechano-regulated proteins YAP and TAZ in promoting gut regeneration in patients with inflammatory bowel disease (IBD). The study found that alterations in mechanotransduction can impact gut regeneration, with mechano-stimulatory drugs aiding regeneration and low mechanical treatments exacerbating gut injury. The researchers also identified the importance of smooth muscle cells' WNT4 in gut regeneration and the role of YAP/TAZ in regulating WNT4 levels. The study suggests that mechanotransduction promotes gut regeneration through the YAP/TAZ-WNT4 signaling axis. [Extracted from the article]

Introduction The aorta and its major side branches are nonredundant for host survival and are protected against inflammatory attack; an immune privilege broken in the case of vasculitis (1). In [...], The aorta and the large conductive arteries are immunoprivileged tissues and are protected against inflammatory attack. A breakdown of immunoprivilege leads to autoimmune vasculitis, such as giant cell arteritis, in which [CD8.sup.+] Treg cells fail to contain [CD4.sup.+] T cells and macrophages, resulting in the formation of tissue-destructive granulomatous lesions. Here, we report that the molecular defect of malfunctioning [CD8.sup.+] Treg cells lies in aberrant NOTCH4 signaling that deviates endosomal trafficking and minimizes exosome production. By transcriptionally controlling the profile of RAB GTPases, NOTCH4 signaling restricted vesicular secretion of the enzyme NADPH oxidase 2 (NOX2). Specifically, [NOTCH4.sup.hi][CD8.sup.+] Treg cells increased RAB5A and RAB11A expression and suppressed RAB7A, culminating in the accumulation of early and recycling endosomes and sequestering of NOX2 in an intracellular compartment. [RAB7A.sup.lo][CD8.sup.+] Treg cells failed in the surface translocation and exosomal release of NOX2. [NOTCH4.sup.hi][RAB5A.sup.hi][RAB7A.sup.lo][RAB11A.sup.hi][CD8.sup.+] Treg cells left adaptive immunity unopposed, enabling a breakdown in tissue tolerance and aggressive vessel wall inflammation. Inhibiting NOTCH4 signaling corrected the defect and protected arteries from inflammatory insult. This study implicates NOTCH4-dependent transcriptional control of RAB proteins and intracellular vesicle trafficking in autoimmune disease and in vascular inflammation.

Introduction The immune system has evolved to protect the host against pathogens and cancerous cells, while keeping tissue-damaging inflammation at a minimum (1). Tregs serve the imperative role of dampening [...], Immune aging results in progressive loss of both protective immunity and T cell-mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive [CD8.sup.+][CCR7.sup.+] Tregs, a defect that is even more pronounced in the agerelated vasculitic syndrome giant cell arteritis. In young, healthy individuals, [CD8.sup.+][CCR7.sup.+] Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis.

Objective: Takayasu arteritis (TAK) is a progressive autoimmune large vessel vasculitis with infiltration of proinflammatory T cells, with a largely unknown etiology. This study was undertaken to explore the involvement of mechanistic target of rapamycin (mTOR) in proinflammatory T cell differentiation and disease progression in TAK. Methods: Ninety‐five patients with TAK, 26 patients with small vessel vasculitis, and 40 healthy donors were enrolled. Naive and memory CD4+ T cells were activated with anti‐CD3/CD28 beads and analyzed for lineage differentiation. The mTORC1 activity was determined by quantifying intracellular phospho–S6 kinase 1 and phospho–S6 ribosomal protein. Rapamycin and lentiviral regulatory‐associated protein of mTOR short hairpin RNA were used to block mTORC1 activity. Human artery–NSG mouse chimeras representing human TAK were established for targeting mTORC1 in disease treatment. Results: TAK CD4+ T cells were selectively prepositioned with hyperactivity of mTORC1 (P < 0.001), resulting in spontaneous maldifferentiation of Th1 and Th17 cells (P < 0.001). Activity of mTORC1high in circulating CD4+ T cells predicted elevated frequencies of proinflammatory T cells and active disease in TAK patients (P < 0.001). Blockade of mTORC1 with rapamycin efficiently abrogated the maldifferentiation of Th1 and Th17 cells (P < 0.01) and ameliorated vasculitis in humanized TAK chimeras (P < 0.001). Inhibition of mTORC1 using RNA interference technology is sufficient to reduce proinflammatory T cell frequencies (P < 0.01) and restrict TAK disease progression in vivo (P < 0.01). Conclusion: Our findings indicate that hyperactivity of mTORC1 is a critical cell‐intrinsic mechanism underlying spontaneous maldifferentiation of proinflammatory T cells in TAK patients. Targeting mTORC1 is a promising therapeutic strategy against TAK. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment.Methods: Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs.Results: Serum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity.Conclusions: IL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients. [ABSTRACT FROM AUTHOR]

Recent evidence showed that limited activation of PI3K/Akt pathway was critical for induction and function sustainment of CD4+Foxp3+ regulatory T cells (Tregs). However, the underlying mechanism remains largely unknown. In this study, we reported that miR-126 was expressed in mouse and human Tregs. Further study showed that silencing of miR-126 using miR-126 antisense oligonucleotides ( ASO) could significantly reduce the induction of Tregs in vitro. Furthermore, miR-126 silencing could obviously reduce the expression of Foxp3 on Tregs, which was accompanied by decreased expression of CTLA-4 and GITR, as well as IL-10 and TGF-β, and impair its suppressive function. Mechanistic evidence showed that silencing of miR-126 enhanced the expression of its target p85β and subsequently altered the activation of PI3K/Akt pathway, which was ultimately responsible for reduced induction and suppressive function of Tregs. Finally, we further revealed that miR-126 silencing could impair the suppressive function of Tregs in vivo and endow effectively antitumour effect of CD8+T cells in adoptive cell transfer assay using a murine breast cancer model. Therefore, our study showed that miR-126 could act as fine-tuner in regulation of PI3K-Akt pathway transduction in the induction and sustained suppressive function of Tregs and provided a novel insight into the development of therapeutic strategies for promoting T-cell immunity by regulating Tregs through targeting specific mi RNAs. [ABSTRACT FROM AUTHOR]