Journal article

Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis

Tom Sidwell, Yang Liao, Alexandra L Garnham, Ajithkumar Vasanthakumar, Renee Gloury, Jonas Blume, Peggy P Teh, David Chisanga, Christoph Thelemann, Fabian de Labastida Rivera, Christian R Engwerda, Lynn Corcoran, Kohei Kometani, Tomohiro Kurosaki, Gordon K Smyth, Wei Shi, Axel Kallies

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract. Bach2 attenuates TCR signaling-induced IRF4-dependent Treg cell differentiation. Deletion of IRF4 promotes inducible Treg cell differentia..

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Grants

Funding Acknowledgements

This work was funded by the National Health and Medical Research Council (project grants and fellowship to A.K., program grant and fellowship to C.E., L.C., G.S.), the Deutsche Forschungsgemeinschaft (fellowship to J.B.), the Schweizer Nationalfond (fellowship to C.T.), Kidney Health Australia (scholarship to P.P.T.), and the Sylvia and Charles Viertel Foundation (fellowship to A.K.). We thank Andrew Lew (The Walter and Eliza Hall Institute of Medical Research) and Kazuhiko Igarashi (Tohoku University) for reagents and mice.