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Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells following Salmonella infection.

Abstract：

:FoxP3+ regulatory T cells (Tregs) control inflammation and maintain mucosal homeostasis, but their functions during infection are poorly understood. Th1, Th2, and Th17 cells can be identified by master transcription factors (TFs) T-bet, GATA3, and RORγT; Tregs also express these TFs. While T-bet+ Tregs can selectively suppress Th1 cells, it is unclear whether distinct Treg populations can alter Th bias. To address this, we used Salmonella enterica serotype Typhimurium to induce nonlethal colitis. Following infection, we observed an early colonic Th17 response within total CD4 T cells, followed by a Th1 bias. The early Th17 response, which contains both Salmonella-specific and non-Salmonella-specific cells, parallels an increase in T-bet+ Tregs. Later, Th1 cells and RORγT+ Tregs dominate. This reciprocal dynamic may indicate that Tregs selectively suppress Th cells, shaping the immune response. Treg depletion 1-2 days post-infection shifted the early Th17 response to a Th1 bias; however, Treg depletion 6-7 days post-infection abrogated the Th1 bias. Thus, Tregs are necessary for the early Th17 response, and for a maximal Th1 response later. These data show that Tregs shape the overall tissue CD4 T cell response and highlight the potential for subpopulations of Tregs to be used in targeted therapeutic approaches.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Clay SL,Bravo-Blas A,Wall DM,MacLeod MKL,Milling SWF

doi

10.1038/s41385-020-0299-1

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

946-957

issue

6

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-020-0299-1

journal_volume

13

pub_type

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