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IRF1 and BATF—transcription factors that set the epigenetic landscape for Tr1 cell differentiation?

Cellular & Molecular Immunology volume 14, pages 727–729 (2017)Cite this article

Type 1 regulatory T (Tr1) cells are Foxp3-negative regulatory CD4+ T cells that develop outside of the thymus and mediate regulatory functions in large part by producing the immunosuppressive cytokine IL-10. They have been shown to play an important role in controlling unwanted immune reactions driven by effector CD4+ and CD8+ T cells, such as those in certain autoimmune diseases and graft-versus-host disease (reviewed in1). These promising results have prompted scientists to test the immunomodulatory potential of these cells in clinical settings by adoptively transferring them into patients who receive hematopoietic stem cells.2 However, although Tr1 cells were first described several decades ago and represent a powerful tool for cell therapies, it is still not resolved whether they represent a distinct T-helper subset or lineage and how they develop. Tr1 cells, at least in vitro, can be induced by several cytokines. In addition to IL-10 itself,3 type 1 interferons4, 5 and IL-276, 7, 8 have been described as potent Tr1 cell inducers. Thus, Tr1 cells may represent another example of apparent T-helper cell plasticity, which may contrast with the existence of a ‘master switch’ TF that regulates their differentiation. Regardless of the Tr1 cell priming cytokine, they all induce IL-10 release, which points to a common or similar transcriptional network that controls their differentiation and remains to be elucidated.

In a recent publication in Nature Immunology, Karwacz et al.,9 sought to identify ‘pioneering factors’ that are induced upon IL-27 stimulation and shape the epigenetic landscape to increase chromatin accessibility and allow the recruitment of additional transcription factors (TFs) during Tr1 cell differentiation.9

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Authors and Affiliations

  1. Charité—Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Augustenburger Platz 1, Berlin, 13353, Germany

    Katarina Stanko & Birgit Sawitzki

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  1. Katarina Stanko
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Correspondence to Birgit Sawitzki.

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Stanko, K., Sawitzki, B. IRF1 and BATF—transcription factors that set the epigenetic landscape for Tr1 cell differentiation?. Cell Mol Immunol 14, 727–729 (2017). https://doi.org/10.1038/cmi.2017.50

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