Transforming Growth Factor-β Signaling in Regulatory T Cells Controls T Helper-17 Cells and Tissue-Specific Immune Responses

Publication date: 18 April 2017
Source:Immunity, Volume 46, Issue 4
Author(s): Joanne E. Konkel, Dunfang Zhang, Peter Zanvit, Cheryl Chia, Tamsin Zangarle-Murray, Wenwen Jin, Songlin Wang, WanJun Chen
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.

Teaser

The role of TGF-β in supporting differentiated Treg cells remains unaddressed. Konkel et al. demonstrate vital roles for TGF-β signals in reinforcing specific Treg cell functions. TGF-β signals limit Treg suppression of Th1-responses but are key for Treg cell function in the colon, revealing unrecognized roles for TGF-β in controlling Treg cell activity in specific tissues.


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