{"title":"Intestinal tissue-resident memory T cells: Characteristics, functions under physiological and pathological conditions and spatial specificity","authors":"Ruochen Yan, Dingjiacheng Jia, Yadong Qi, Qiwen Wang, Shujie Chen","doi":"10.1016/j.jare.2025.03.021","DOIUrl":null,"url":null,"abstract":"<h3>Background</h3>Tissue-resident memory T (T<sub>RM</sub>) cells are a distinct subset of memory T cells that persist in non-lymphoid tissues, providing localized and rapid immune responses to infection and malignancy. Unlike circulating memory T cells, T<sub>RM</sub> cells have unique homing and functional characteristics that are shaped by the tissue microenvironment. In the gut, T<sub>RM</sub> cells play a pivotal role in maintaining mucosal immunity, exhibiting phenotypic and functional heterogeneity in different intestinal compartments and in response to aging and pathological conditions.<h3>Aim of review</h3>This review aims to systematically examine the definition, spatial heterogeneity and functional roles of intestinal T<sub>RM</sub> (iT<sub>RM</sub>) cells. It highlights their contributions to physiological immunity, their involvement in pathological processes such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), and their age-related dynamics. The review also explores emerging therapeutic implications of modulating iT<sub>RM</sub> cells for intestinal health and disease management.<h3>Key scientific concepts of review</h3>iT<sub>RM</sub> cells are defined by surface markers like CD69 and CD103, transcriptional regulators such as Hobit, Runx3, Blimp-1, as well as cytokine signals including TGF-β, IFN-β, IL-12. They exhibit spatial and functional heterogeneity across intestinal layers (epithelium versus lamina propria) and regions (small intestine versus colon). In IBD, iT<sub>RM</sub> cells play a dual role, contributing to both inflammation and tissue repair, whereas in CRC, specific subsets of iT<sub>RM</sub> cells (e.g., CD8<sup>+</sup> CD103<sup>+</sup> CD39<sup>+</sup>) are associated with enhanced antitumor immunity. Aging impacts iT<sub>RM</sub> functionality, with shifts in the CD4<sup>+</sup>/CD8<sup>+</sup> ratio and reduced cytokine production in elderly individuals. Insights into the metabolic, transcriptional, and environmental regulation of iT<sub>RM</sub> cells provide avenues for targeted therapies in intestinal diseases, cancer immunotherapy, and interventions to delay intestinal aging.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"56 1","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Advanced Research","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.jare.2025.03.021","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Tissue-resident memory T (TRM) cells are a distinct subset of memory T cells that persist in non-lymphoid tissues, providing localized and rapid immune responses to infection and malignancy. Unlike circulating memory T cells, TRM cells have unique homing and functional characteristics that are shaped by the tissue microenvironment. In the gut, TRM cells play a pivotal role in maintaining mucosal immunity, exhibiting phenotypic and functional heterogeneity in different intestinal compartments and in response to aging and pathological conditions.
Aim of review
This review aims to systematically examine the definition, spatial heterogeneity and functional roles of intestinal TRM (iTRM) cells. It highlights their contributions to physiological immunity, their involvement in pathological processes such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), and their age-related dynamics. The review also explores emerging therapeutic implications of modulating iTRM cells for intestinal health and disease management.
Key scientific concepts of review
iTRM cells are defined by surface markers like CD69 and CD103, transcriptional regulators such as Hobit, Runx3, Blimp-1, as well as cytokine signals including TGF-β, IFN-β, IL-12. They exhibit spatial and functional heterogeneity across intestinal layers (epithelium versus lamina propria) and regions (small intestine versus colon). In IBD, iTRM cells play a dual role, contributing to both inflammation and tissue repair, whereas in CRC, specific subsets of iTRM cells (e.g., CD8+ CD103+ CD39+) are associated with enhanced antitumor immunity. Aging impacts iTRM functionality, with shifts in the CD4+/CD8+ ratio and reduced cytokine production in elderly individuals. Insights into the metabolic, transcriptional, and environmental regulation of iTRM cells provide avenues for targeted therapies in intestinal diseases, cancer immunotherapy, and interventions to delay intestinal aging.
期刊介绍:
Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences.
The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.