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

Sci Signal. 2018 Aug 28;11(545):eaar2125. doi: 10.1126/scisignal.aar2125.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / immunology*
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / immunology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors, Type I