Research ArticleT CELLS

TGF-β–mediated enhancement of TH17 cell generation is inhibited by bone morphogenetic protein receptor 1α signaling

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Sci. Signal.  28 Aug 2018:
Vol. 11, Issue 545, eaar2125
DOI: 10.1126/scisignal.aar2125

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BMPing up against TGF-β

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor–β (TGF-β) family of cytokines. Within this family, TGF-β is critical to prevent the spontaneous activation of self-reactive T cells and promote the differentiation of T helper 17 (TH17) cells. Browning et al. found that the CD4+ T cell–intrinsic activation of BMP receptor 1α inhibited the differentiation of CD4+ T cells into TH17 cells. Loss of this receptor reprogrammed the transcriptome of effector T cells, promoted exaggerated responses to inflammatory cytokines, and exacerbated disease in a mouse model of colitis. These data suggest that BMPs may antagonize TGF-β to limit effector T cell development and function.

Abstract

The cytokines of the transforming growth factor–β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells and sustain immune homeostasis. In contrast, in the presence of proinflammatory cytokines, TGF-β promotes the differentiation of effector T helper 17 (TH17) cells. Abrogating TGF-β receptor signaling prevents the development of interleukin-17 (IL-17)–secreting cells and protects mice from TH17 cell–mediated autoimmunity. We found that the receptor of another member of TGF-β family, bone morphogenetic protein receptor 1α (BMPR1α), regulates T helper cell activation. We found that the differentiation of TH17 cells from naive CD4+ T cells was inhibited in the presence of BMPs. Abrogation of BMPR1α signaling during CD4+ T cell activation induced a developmental program that led to the generation of inflammatory effector cells expressing large amounts of IL-17, IFN-γ, and TNF family cytokines and transcription factors defining the TH17 cell lineage. We found that TGF-β and BMPs cooperated to establish effector cell functions and the cytokine profile of activated CD4+ T cells. Together, our data provide insight into the immunoregulatory function of BMPs.

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