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

The cytokines of the transforming growth factor-beta (TGF-beta) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-beta, in regulating the immune responses has been extensively studied. TGF-beta 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-beta promotes the differentiation of effector T helper 17 (T(H)17) cells. Abrogating TGF-beta receptor signaling prevents the development of interleukin-17 (IL-17)-secreting cells and protects mice from T(H)17 cell-mediated autoimmunity. We found that the receptor of another member of TGF-beta family, bone morphogenetic protein receptor 1 alpha (BMPR1 alpha), regulates T helper cell activation. We found that the differentiation of T(H)17 cells from naive CD4(+) T cells was inhibited in the presence of BMPs. Abrogation of BMPR1 alpha 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-gamma, and TNF family cytokines and transcription factors defining the T(H)17 cell lineage. We found that TGF-beta 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.