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

Clay, S. L. , Bravo-Blas, A., Wall, D. M. , MacLeod, M. K.L. and Milling, S. W.F. (2020) Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells following Salmonella infection. Mucosal Immunology, 13(6), pp. 946-957. (doi: 10.1038/s41385-020-0299-1) (PMID:32457450) (PMCID:PMC7567643)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bravo-Blas, Dr Alberto and Macleod, Dr Megan and Milling, Professor Simon and Wall, Dr Daniel and Clay, Slater
• Authors: Clay, S. L., Bravo-Blas, A., Wall, D. M., MacLeod, M. K.L., and Milling, S. W.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Mucosal Immunology
• Publisher: Nature Research
• ISSN: 1933-0219
• ISSN (Online): 1935-3456
• Published Online: 26 May 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Mucosal Immunology 13(6): 946-957
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172896		Defining mechanisms that control T cell migration	Simon Milling	Medical Research Council (MRC)	MR/N023625/1	III - Immunology