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 (T_H17) cells. Abrogating TGF-β receptor signaling prevents the development of interleukin-17 (IL-17)–secreting cells and protects mice from T_H17 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 T_H17 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 T_H17 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.

转化生长因子-β (TGF-β) 家族的细胞因子促进多种组织的生长和分化，但只有创始成员 TGF-β 在调节免疫反应中的作用已得到广泛研究。TGF-β 对于防止自反应性 T 细胞的自发激活和维持免疫稳态至关重要。相反，在促炎细胞因子存在的情况下，TGF-β 促进效应 T 辅助 17 (T _H 17) 细胞的分化。消除 TGF-β 受体信号可防止白细胞介素 17 (IL-17) 分泌细胞的发育并保护小鼠免受 T _H17 细胞介导的自身免疫。我们发现 TGF-β 家族的另一个成员骨形态发生蛋白受体 1α (BMPR1α) 的受体调节 T 辅助细胞的活化。我们发现 T _H 17 细胞从初始 CD4 ⁺ T 细胞分化在 BMP 存在下受到抑制。在 CD4 ⁺ T 细胞激活期间取消 BMPR1α 信号传导诱导了一个发育程序，该程序导致产生表达大量 IL-17、IFN-γ 和 TNF 家族细胞因子和转录因子的炎症效应细胞，这些细胞因子和转录因子定义了 T _H 17 细胞谱系。我们发现 TGF-β 和 BMPs 合作建立效应细胞功能和活化 CD4 ⁺的细胞因子谱T细胞。总之，我们的数据提供了对 BMP 免疫调节功能的深入了解。