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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.

Objective: To explore T cell‐intrinsic mechanisms underpinning the mal‐differentiation of tissue‐resident memory T (Trm) cells in patients with rheumatoid arthritis (RA). Methods: Circulating T cells from patient with RA and healthy individuals were used for Trm cell differentiation. The role of Hobit in Trm differentiation was investigated through targeted silencing experiments. Psmb5 expression regulation was explored by identifying BRD2 as a key transcription factor, with the interaction validated through chromatin immunoprecipitation‐quantitative polymerase chain reaction. The impact of BRD2 succinylation on Trm differentiation was examined by manipulating succinyl‐CoA levels in T cells. Humanized NSG chimeras representing synovitis provided insights into Trm infiltration in RA synovitis and were used for translational experiments. Results: In patients with RA, a notable predisposition of CD4+ T cells toward differentiation into Trm cells was observed, demonstrating a positive correlation with the disease activity score 28. Remarkably, Hobit was a pivotal facilitator in the formation of RA CD4+ Trm cells. Mechanistic studies unveiled the dysregulation of proteasomal Psmb5 in T cells of patients with RA as the key factor contributing to elevated Hobit protein levels. The deficiency of proteasomal Psmb5 was intricately linked to BRD2, with succinylation exerting a significant impact on Psmb5 transcription and Trm cell differentiation. This heightened BRD2 succinylation was attributed to elevated levels of mitochondrial succinyl‐CoA in RA T cells. Consequently, targeting succinyl‐CoA within CD4+ T cells controlled the inflammation of synovial tissues in humanized chimeras. Conclusion: Mitochondrial succinyl‐CoA fosters the succinylation of BRD2, resulting in compromised transcription of proteasomal Psmb5 and the differentiation of Trm cells in RA. [ABSTRACT FROM AUTHOR]

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]

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 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 [...]

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., 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 [...]

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]