Intestinal tissue-resident memory T cells: Characteristics, functions under physiological and pathological conditions and spatial specificity

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Tissue-resident memory T (TRM) cells are a distinct subset of that persist in non-lymphoid tissues, providing localized and rapid immune responses to infection malignancy. Unlike circulating cells, TRM have unique homing functional characteristics shaped by the tissue microenvironment. In gut, play pivotal role maintaining mucosal immunity, exhibiting phenotypic heterogeneity different intestinal compartments response aging pathological conditions. This review aims systematically examine definition, spatial roles (iTRM) cells. It highlights their contributions physiological involvement processes such as inflammatory bowel disease (IBD) colorectal cancer (CRC), age-related dynamics. The also explores emerging therapeutic implications modulating iTRM for health management. KEY SCIENTIFIC CONCEPTS OF REVIEW: defined surface markers like CD69 CD103, transcriptional regulators Hobit, Runx3, Blimp-1, well cytokine signals including TGF-β, IFN-β, IL-12. They exhibit across layers (epithelium versus lamina propria) regions (small intestine colon). IBD, dual role, contributing both inflammation repair, whereas CRC, specific subsets (e.g., CD8+ CD103+ CD39+) associated with enhanced antitumor immunity. Aging impacts functionality, shifts CD4+/CD8+ ratio reduced production elderly individuals. Insights into metabolic, transcriptional, environmental regulation provide avenues targeted therapies diseases, immunotherapy, interventions delay aging.

Language: Английский

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Multiplexed in vivo base editing identifies functional gene-variant-context interactions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Human genome sequencing efforts in healthy and diseased individuals continue to identify a broad spectrum of genetic variants associated with predisposition, progression, therapeutic outcomes for diseases like cancer 1-6 . Insights derived from these studies have significant potential guide clinical diagnoses treatment decisions; however, the relative importance functional impact most remain poorly understood. Precision editing technologies base prime can be used systematically engineer interrogate diverse types endogenous their native context 7-9 We others recently developed applied scalable sensor-based screening approaches measure phenotypes produced by thousands mutations vitro 10-12 However, physiological vivo setting, including contextual differences depending on tissue or microenvironment, remains unexplored. Here, we integrate new cross-species sensor libraries syngeneic mouse models develop multiplexed platform systematic analysis primary disseminated malignancies. this screen 13,840 RNAs designed 7,783 human cancer-associated mapping 489 protein-coding genes, allowing us construct rich compendium putative interactions between mutations, contexts. Our findings suggest that environment cellular organotropism are important determinants specific gene-variant phenotypes. also show many effects fail detected standard CRISPR-Cas9 nuclease often produce discordant phenotypes, potentially due site-specific amino acid selection- separation-of-function mechanisms. This versatile could deployed investigate how variation impacts other diseases, as well avenues treat disease.

Language: Английский

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Angel and devil: the protective immunity and pathogenic inflammation of tissue resident memory T cells in ulcerative colitis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Ulcerative colitis (UC) is an incurable autoimmune disease. Patients with UC endure the burden of recurrent flare-ups and face a substantial economic due to long-term medication. The complex etiology unclear pathogenesis pose significant challenge development effective curative treatments. Recent research indicates that local memory at site inflammatory intestinal mucosa in closely associated persistent presence tissue-resident T (TRM) cells. TRM cells, subset exhibit long-lived, low-migration characteristics. These cells reside tissues, where they provide immediate immune protection while also contributing chronic, localized inflammation. inflamed patients crucial factor recurrence However, process involved formation differentiation within remains poorly understood. Various surface markers, transcriptional networks, signaling pathways regulate maintenance intestine. To further understand role pathogenesis, we have summarized latest findings pave way for future targeted therapies.

Language: Английский

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Identification of Senescence-Related Genes for the Prediction of Ulcerative Colitis Based on Interpretable Machine Learning Models

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3431 - 3447

Published: March 1, 2025

Background: Cellular senescence, a hallmark of aging, significantly contributes to the pathology ulcerative colitis (UC). Despite this, role senescence-related genes in UC remains largely undefined. This study seeks clarify impact cellular senescence on by identifying key and developing diagnostic models with potential clinical utility. Methods: Clinical data gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. Senescence-related differentially expressed (sene-DEGs) between patients healthy controls identified using various bioinformatics techniques. Functional enrichment immune infiltration analyses performed understand subtype characteristics derived sene-DEGs through consensus clustering. Machine learning algorithms employed select feature sene-DEGs, their was validated across multiple independent datasets human specimens. A nomogram incorporating these created assessed, its performance evaluated receiver operating characteristic (ROC) analysis datasets. Results: Fourteen differential controls. These enabled classification into molecular subtypes via unsupervised ABCB1 LCN2 emerged as central hub machine importance analysis. ROC verified value Validation specimens supported findings. Furthermore, levels showed significant associations cell profiles. The logistic regression (LR) model based demonstrated accurate prediction, confirmed curve model, constructed genes, exhibited outstanding prediction capabilities, DCA, C index, calibration assessments. Conclusion: integrated approach biomarkers associated senescence. findings enhance understanding pathogenesis propose valuable biomarker. Keywords: colitis, biomarkers,

Language: Английский

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Home at last: Mixed signals guide memory T cells to residency

Immunity, Journal Year: 2024, Volume and Issue: 57(11), P. 2486 - 2488

Published: Nov. 1, 2024

Language: Английский

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