Journal article
c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis
C Neumann, J Blume, U Roy, PP Teh, A Vasanthakumar, A Beller, Y Liao, F Heinrich, TL Arenzana, JA Hackney, C Eidenschenk, EJC Gálvez, C Stehle, GA Heinz, P Maschmeyer, T Sidwell, Y Hu, D Amsen, C Romagnani, HD Chang Show all
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2019
Abstract
Foxp3+ regulatory T cells (Treg cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal Treg cells to constrain microbiota-dependent interleukin (IL)-17–producing helper T cell (TH17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal Treg cell populations, including RORγt+ Treg cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled Treg cell–derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This research was supported by the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy-EXC 2167-390884018 (to A.S.), SFB650 (to A.S.) and CRC/TR 241 (to A.S. and C.R.), the German Federal Ministry of Education and Science (BMBF)-Project InfectControl 2020 Projekt DIAT FKZ: 03ZZ0827A (to A.S.), the state of Berlin and the 'European Regional Development Fund' ERDF 2014-2020, EFRE 1.8/11, Deutsches Rheuma-Forschungszentrum (to F.H., G.A.H, P.M. and M.F.M), the Helmholtz Association project grant VH-NG-933 (to T. Strowig), the National Health and Medical Research Council (NHMRC) project grants (1069075, 1106378 to A. Kallies), the Sylvia and Charles Viertel Foundation (fellowship to A. Kallies), a Walter and Eliza Institute Centenary Fellowship funded by the CSL (to W.S.), a fellowship by the Deutsche Forschungsgemeinschaft (to J.B.) and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. We thank the DRFZ Flow Cytometry Core Facility and the BCRT Flow Cytometry Lab for cell sorting. In addition, we thank Renee Gloury and Victoria von Gotze for technical and experimental help.