TY - JOUR
T1 - Transforming growth factor–β1 in regulatory T cell biology
AU - Moreau, Joshua M.
AU - Velegraki, Maria
AU - Bolyard, Chelsea
AU - Rosenblum, Michael D.
AU - Li, Zihai
N1 - Publisher Copyright:
© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.
PY - 2022/3
Y1 - 2022/3
N2 - Transforming growth factor–β1 (TGF-β1) is inextricably linked to regulatory T cell (Treg) biology. However, precisely untangling the role for TGF-β1 in Treg differentiation and function is complicated by the pleiotropic and context-dependent activity of this cytokine and the multifaceted biology of Tregs. Among CD4+ T cells, Tregs are the major producers of latent TGF-β1 and are uniquely able to activate this cytokine via expression of cell surface docking receptor glycoprotein A repetitions predominant (GARP) and αv integrins. Although a preponderance of evidence indicates no essential roles for Treg-derived TGF-β1 in Treg immunosuppression, TGF-β1 signaling is crucial for Treg development in the thymus and periphery. Furthermore, active TGF-β1 instructs the differentiation of other T cell subsets, including TH17 cells. Here, we will review TGF-β1 signaling in Treg development and function and discuss knowledge gaps, future research, and the TGF-β1/Treg axis in the context of cancer immunotherapy and fibrosis.
AB - Transforming growth factor–β1 (TGF-β1) is inextricably linked to regulatory T cell (Treg) biology. However, precisely untangling the role for TGF-β1 in Treg differentiation and function is complicated by the pleiotropic and context-dependent activity of this cytokine and the multifaceted biology of Tregs. Among CD4+ T cells, Tregs are the major producers of latent TGF-β1 and are uniquely able to activate this cytokine via expression of cell surface docking receptor glycoprotein A repetitions predominant (GARP) and αv integrins. Although a preponderance of evidence indicates no essential roles for Treg-derived TGF-β1 in Treg immunosuppression, TGF-β1 signaling is crucial for Treg development in the thymus and periphery. Furthermore, active TGF-β1 instructs the differentiation of other T cell subsets, including TH17 cells. Here, we will review TGF-β1 signaling in Treg development and function and discuss knowledge gaps, future research, and the TGF-β1/Treg axis in the context of cancer immunotherapy and fibrosis.
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U2 - 10.1126/sciimmunol.abi4613
DO - 10.1126/sciimmunol.abi4613
M3 - Review article
C2 - 35302863
AN - SCOPUS:85126654841
SN - 2470-9468
VL - 7
JO - Science Immunology
JF - Science Immunology
IS - 69
M1 - eabi4613
ER -