| First Author | Browning LM | Year | 2018 |
| Journal | Sci Signal | Volume | 11 |
| Issue | 545 | PubMed ID | 30154100 |
| Mgi Jnum | J:281783 | Mgi Id | MGI:6380742 |
| Doi | 10.1126/scisignal.aar2125 | Citation | Browning LM, et al. (2018) TGF-beta-mediated enhancement of TH17 cell generation is inhibited by bone morphogenetic protein receptor 1alpha signaling. Sci Signal 11(545) |
| abstractText | 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 (TH17) cells. Abrogating TGF-beta 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-beta family, bone morphogenetic protein receptor 1alpha (BMPR1alpha), 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 BMPR1alpha 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 TH17 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. |
