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Activin A programs the differentiation of human T-FH cells

机译：激活素A编程人T-FH细胞的分化

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Follicular helper T cells (T-FH 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 T-FH cells therapeutically has been limited by fragmentary understanding of extrinsic signals that regulate the differentiation of human T-FH cells. A screen of a human protein library identified activin A as a potent regulator of T-FH cell differentiation. Activin A orchestrated the expression of multiple genes associated with the T-FH program, independently or in concert with additional signals. T-FH cell programming by activin A was antagonized by the cytokine IL-2. Activin A's ability to drive T-FH cell differentiation in vitro was conserved in non-human primates but not in mice. Finally, activin-A-induced T-FH programming was dependent on signaling via SMAD2 and SMAD3 and was blocked by pharmacological inhibitors.
机译：滤泡辅助性T细胞（T-FH细胞）是专门帮助B细胞的CD4（+）T细胞，与保护性抗体应答和自身免疫性疾病均相关。治疗性靶向T-FH细胞的前景受到了对调节人T-FH细胞分化的外源信号的零碎理解的限制。人类蛋白质文库的筛选确定了激活素A是T-FH细胞分化的有效调节剂。激活素A独立或与其他信号协同调节与T-FH程序相关的多个基因的表达。通过激活素A对T-FH细胞的编程被细胞因子IL-2拮抗。活化素A在体外驱动T-FH细胞分化的能力在非人类灵长类动物中得以保留，但在小鼠中却没有。最后，激活素A诱导的T-FH编程取决于通过SMAD2和SMAD3发出的信号，并被药理抑制剂所阻断。

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