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

被引:14
|
作者
Browning, Lauren M. [1 ]
Pietrzak, Maciej [2 ]
Kuczma, Michal [3 ]
Simms, Colin P. [1 ]
Kurczewska, Agnieszka [1 ]
Refugia, Justin M. [1 ]
Lowery, Dustin J. [1 ]
Rempala, Grzegorz [4 ]
Gutkin, Dmitriy [5 ]
Ignatowicz, Leszek [3 ]
Muranski, Pawel [6 ]
Kraj, Piotr [1 ]
机构
[1] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA
[2] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA
[3] Georgia State Univ, Inst Biomed Sci, Atlanta, GA 30303 USA
[4] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA
[5] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15240 USA
[6] Columbia Univ, Med Ctr, New York, NY 10032 USA
关键词
REGULATORY T-CELLS; IN-VIVO; AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTIONAL SIGNATURE; INTESTINAL INFLAMMATION; HELPER-CELLS; TH17; CELLS; DIFFERENTIATION; SPECIFICITY; RESPONSES;
D O I
10.1126/scisignal.aar2125
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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