TY - JOUR
T1 - Transforming Growth Factor-β Signaling in Regulatory T Cells Controls T Helper-17 Cells and Tissue-Specific Immune Responses
AU - Konkel, Joanne E.
AU - Zhang, Dunfang
AU - Zanvit, Peter
AU - Chia, Cheryl
AU - Zangerle Murray, Tamsin
AU - Jin, Wenwen
AU - Wang, Songlin
AU - Chen, Wan Jun
PY - 2017/4
Y1 - 2017/4
N2 - Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-β (TGF-β) signals in safe-guarding specific Treg cell functions. TGF-β signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells require TGF-β signals to appropriately dampen Th17 cells and regulate responses in the gastrointestinal tract. TGF-β signaling maintains CD103 expression, promotes expression of the colon-specific trafficking molecule GPR15, and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg cells, collectively supporting the accumulation and retention of Treg cells in the colon and control of colitogenic responses. Thus, we reveal an unrecognized function for TGF-β signaling as an upstream factor controlling Treg cell activity in specific tissue environments.
AB - Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-β (TGF-β) signals in safe-guarding specific Treg cell functions. TGF-β signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells require TGF-β signals to appropriately dampen Th17 cells and regulate responses in the gastrointestinal tract. TGF-β signaling maintains CD103 expression, promotes expression of the colon-specific trafficking molecule GPR15, and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg cells, collectively supporting the accumulation and retention of Treg cells in the colon and control of colitogenic responses. Thus, we reveal an unrecognized function for TGF-β signaling as an upstream factor controlling Treg cell activity in specific tissue environments.
UR - http://www.scopus.com/inward/record.url?scp=85019022332&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2017.03.015
DO - 10.1016/j.immuni.2017.03.015
M3 - Article
AN - SCOPUS:85019022332
SN - 1074-7613
VL - 46
SP - 660
EP - 674
JO - Immunity
JF - Immunity
IS - 4
ER -
