Research ArticleIMMUNE REGULATION

Eomesodermin promotes the development of type 1 regulatory T (TR1) cells

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Science Immunology  07 Apr 2017:
Vol. 2, Issue 10, eaah7152
DOI: 10.1126/sciimmunol.aah7152

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Regulatory T cells sans FoxP3

Although expression of FoxP3 is largely synonymous with regulatory T (Treg) cell identity in mice, type 1 regulatory T (TR1) cells are an exception. TR1 cells produce interleukin-10 but are FoxP3. In comparison with FoxP3+ Treg cells, the development and functions of TR1 cells are poorly understood. Here, Zhang et al. report that TR1 cells play a critical regulatory role after allogeneic bone marrow transplantation (BMT) in mice and use this model to delineate the molecular circuits driving commitment to the TR1 cell lineage. By documenting the presence of TR1 cells after BMT in humans, they propose that modulation of TR1 cells could be a therapeutic venue for increasing BMT success rates in the clinic.

Abstract

Type 1 regulatory T (TR1) cells are Foxp3 interleukin-10 (IL-10)–producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.

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