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.
journal_name
Sci Signaljournal_title
Science signalingauthors
Browning LM,Pietrzak M,Kuczma M,Simms CP,Kurczewska A,Refugia JM,Lowery DJ,Rempala G,Gutkin D,Ignatowicz L,Muranski P,Kraj Pdoi
10.1126/scisignal.aar2125subject
Has Abstractpub_date
2018-08-28 00:00:00issue
545eissn
1945-0877issn
1937-9145pii
11/545/eaar2125journal_volume
11pub_type
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