Terminal differentiation and persistence of effector regulatory T cells essential for preventing intestinal inflammation Journal Article

   

Authors:	Dikiy, S.; Ghelani, A. P.; Levine, A. G.; Martis, S.; Giovanelli, P.; Wang, Z. M.; Beroshvili, G.; Pritykin, Y.; Krishna, C.; Huang, X.; Glasner, A.; Greenbaum, B. D.; Leslie, C. S.; Rudensky, A. Y.
Article Title:	Terminal differentiation and persistence of effector regulatory T cells essential for preventing intestinal inflammation
Abstract:	Regulatory T (Treg) cells are a specialized CD4+ T cell lineage with essential anti-inflammatory functions. Analysis of Treg cell adaptations to non-lymphoid tissues that enable their specialized immunosuppressive and tissue-supportive functions raises questions about the underlying mechanisms of these adaptations and whether they represent stable differentiation or reversible activation states. Here, we characterize distinct colonic effector Treg cell transcriptional programs. Attenuated T cell receptor (TCR) signaling and acquisition of substantial TCR-independent functionality seems to facilitate the terminal differentiation of a population of colonic effector Treg cells that are distinguished by stable expression of the immunomodulatory cytokine IL-10. Functional studies show that this subset of effector Treg cells, but not their expression of IL-10, is indispensable for colonic health. These findings identify core features of the terminal differentiation of effector Treg cells in non-lymphoid tissues and their function. © The Author(s) 2025.
Keywords:	signal transduction; mouse; animal; metabolism; animals; mice; mice, knockout; interleukin 10; inflammation; cell differentiation; mice, inbred c57bl; c57bl mouse; regulatory t lymphocyte; immunology; receptors, antigen, t-cell; t-lymphocytes, regulatory; colitis; colon; lymphocyte antigen receptor; knockout mouse; interleukin-10
Journal Title:	Nature Immunology
Volume:	26
Issue:	3
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Date Published:	2025-03-01
Start Page:	444
End Page:	458
Language:	English
DOI:	10.1038/s41590-024-02075-6
PUBMED:	39905200
PROVIDER:	scopus
PMCID:	PMC11876075
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85217996114&doi=10.1038%2fs41590-024-02075-6&partnerID=40&md5=cb91b79519bfc1dd1a175909d0bd010d
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Alexander Rudenski -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/223936