Regulatory T cells (Treg cells) are required for peripheral tolerance. Evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with helper T cell differentiation. Here we demonstrate that expression of the transcription factor Blimp-1 defined a population of Treg cells that localized mainly to mucosal sites and produced IL-10. Blimp-1 was required for IL-10 production by these cells and for their tissue homeostasis. We provide evidence that the transcription factor IRF4, but not the transcription factor T-bet, was essential for Blimp-1 expression and for the differentiation of all effector Treg cells. Thus, our study defines a differentiation pathway that leads to the acquisition of Treg cell effector functions and requires both IRF4 and Blimp-1.
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We thank T. Mak, L. Wu, J. Altin and P. Bouillet for mice; S. Sterle, N. Bernard, R. Thong and K. Elder for technical support; Y. Zhan, I. Campbell and K. Shortman for antibodies; L. Corcoran and D. Tarlinton for discussion and reagents; and Y. Zheng and A. Rudensky for the full microarray data set already published in part17. Supported by the National Health and Medical Research Council of Australia (E.C., G.T.B., S.L.N. and A.K.), L'Oréal Australia For Women in Science Fellowship (E.C.), the Swiss National Science Foundation (F.M.), the Viertel Foundation, the Howard Hughes Medical Institute (G.T.B.), the Pfizer Australia Research Fellowship program (S.L.N.), the Leukemia & Lymphoma Society (A.K.), Boehringer Ingelheim (Busslinger group) and the European Union Sixth Framework Programme FP6 (EuTRACC project, Busslinger group).
The authors declare no competing financial interests.
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Cretney, E., Xin, A., Shi, W. et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat Immunol 12, 304–311 (2011). https://doi.org/10.1038/ni.2006
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