激活素2型受体
细胞分化
ACVR2B型
生物
调节器
激活素受体
细胞生物学
免疫学
转化生长因子β信号通路
信号转导
转化生长因子
基因
遗传学
作者
Michela Locci,Jennifer E. Wu,Fortuna Arumemi,Zbigniew Mikulski,Carol Dahlberg,Andrew T. Miller,Shane Crotty
摘要
Crotty and colleagues identify activin A as a regulator of human TFH cell differentiation. The effects of activin A show evolutionary divergence. Follicular helper T cells (TFH cells) are CD4+ T cells specialized in helping B cells and are associated both with protective antibody responses and autoimmune diseases. The promise of targeting TFH cells therapeutically has been limited by fragmentary understanding of extrinsic signals that regulate the differentiation of human TFH cells. A screen of a human protein library identified activin A as a potent regulator of TFH cell differentiation. Activin A orchestrated the expression of multiple genes associated with the TFH program, independently or in concert with additional signals. TFH cell programming by activin A was antagonized by the cytokine IL-2. Activin A's ability to drive TFH cell differentiation in vitro was conserved in non-human primates but not in mice. Finally, activin-A-induced TFH programming was dependent on signaling via SMAD2 and SMAD3 and was blocked by pharmacological inhibitors.
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