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IRF1 and BATF: key drivers of type 1 regulatory T-cell differentiation

Cellular & Molecular Immunology volume 14, pages 652–654 (2017)Cite this article

It has long been known that T regulatory (Tr)1 cells are required to maintain immune homeostasis, yet little is known about the factors that govern early lineage commitment, including chromatin accessibility for the transcription of genes related to the Tr1 program. In a recent study, Karwacz and colleagues have described key roles of the transcription factors IRF1 and BATF during Tr1 cell differentiation in response to IL-27 signaling. These factors modulate the chromatin landscape during induction of the Tr1 cell program: BATF prepares the binding of transcription factors involved in Tr1 cell lineage commitment, and IRF1 transactivates Il10 gene expression and Tr1 cell-related genes while inhibiting Th17 cell differentiation.

Tr1 cells are a subset of CD4+ T regulatory cells that, in contrast to classical CD4+ T regulatory (Treg) cells, exert a suppressive function that is not associated with the expression of the transcription factor forkhead box P3 (FOXP3).1 Characteristics of Tr1 cells include the co-expression of LAG-3 and CD49b,2 as well as a signature cytokine profile that includes copious secretion of IL10 and less substantial production of TGF-β, IFN-γ and IL-5.3, 4 Although a master transcriptional regulator analogous to FOXP3 in Treg cells has not been identified in Tr1 cells, several mechanisms that regulate Tr1 differentiation have been elucidated. These findings support the potential therapeutic use of Tr1 cells in transplant medicine, in which an expansion of Tr1 cells in mouse models has been reported to successfully induce graft tolerance, or in inflammatory bowel disease, in which clinical trials are underway.5, 6

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  1. Department of Medicine, University of California Los Angeles, Los Angeles, 90095-1670, CA, USA

    Sophia Giang & Antonio La Cava

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  1. Sophia Giang
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Correspondence to Antonio La Cava.

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Giang, S., La Cava, A. IRF1 and BATF: key drivers of type 1 regulatory T-cell differentiation. Cell Mol Immunol 14, 652–654 (2017). https://doi.org/10.1038/cmi.2017.38

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