Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells Journal Article

   

Authors:	van der Veeken, J.; Campbell, C.; Pritykin, Y.; Schizas, M.; Verter, J.; Hu, W.; Wang, Z. M.; Matheis, F.; Mucida, D.; Charbonnier, L. M.; Chatila, T. A.; Rudensky, A. Y.
Article Title:	Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells
Abstract:	Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive T cell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4+ T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms supporting their differentiation remain poorly understood. Here, we used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. Lineage-committed, microbiota-dependent pTreg-like cells persisted in the colon in the absence of Foxp3. While Foxp3 was critical for the suppression of a Th17 cell program, colitis, and mastocytosis, pTreg cells suppressed colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals that precede and promote its expression independently confer distinct facets of pTreg functionality. © 2022
Keywords:	forkhead transcription factors; metabolism; immunological tolerance; regulatory t lymphocyte; immune tolerance; t-lymphocytes, regulatory; th17 cell; forkhead transcription factor; thymocyte; foxp3; th17 cells; thymocytes; microbiota; lineage tracing; treg; peripherally induced treg
Journal Title:	Immunity
Volume:	55
Issue:	7
ISSN:	1074-7613
Publisher:	Cell Press
Date Published:	2022-07-12
Start Page:	1173
End Page:	1184.e7
Language:	English
DOI:	10.1016/j.immuni.2022.05.010
PUBMED:	35700740
PROVIDER:	scopus
PMCID:	PMC9885886
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134297327&doi=10.1016%2fj.immuni.2022.05.010&partnerID=40&md5=94f03ff946dd491ebee630206fbe201e
Notes:	Article -- Export Date: 1 August 2022 -- Source: Scopus

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