The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells.
The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells.
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诱导共刺激分子 (ICOS) 被认为在产生白细胞介素 17 (IL-17) 的 T 辅助细胞 (TH-17 细胞) 和滤泡辅助细胞 (TFH 细胞)、抗体类别转换和生发中心形成所需的特殊辅助 T 细胞 (CD4+CXCR5+ICOShigh) 的发育中发挥重要作用。在这里，我们表明，ICOS 虽然对于 TH-17 细胞的分化不是必需的，但对于维持效应记忆 TH-17 细胞至关重要，因为 ICOS 缺陷的小鼠在 IL-23 刺激后表现出 TH-17 细胞扩增的缺陷。此外，我们发现 TFH 细胞产生 IL-17，并且 ICOS 缺陷小鼠表现出 TFH 频率降低，且 IL-17 产生缺陷。 TH-17 和 TFH 细胞均表现出转录因子 c-Maf 表达增加（通常与 TH2 细胞相关），而 c-Maf 的缺失会导致 IL-21 产生缺陷，从而导致 IL-23R 表达维持和 TH-17 和 TFH 细胞扩增缺陷。这些数据表明，ICOS 诱导的 c-Maf 调节 IL-21 的产生，进而调节 TH-17 细胞和 TFH 细胞的扩增。
The inducible costimulatory molecule (ICOS) has been suggested to play an important role in the development of interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) and of follicular helper cells (TFH cells), specialized helper T cells (CD4+CXCR5+ICOShigh) required for antibody class switching and germinal center formation. Here we show that ICOS, while not essential for the differentiation of TH-17 cells, was critical for maintaining effector-memory TH-17 cells as ICOS-deficient mice demonstrated a defect in the expansion of TH-17 cells after IL-23 stimulation. In addition, we found that TFH cells produced IL-17 and that ICOS-deficient mice demonstrated a reduced frequency of TFH with a defect in IL-17 production. Both TH-17 and TFH cells showed increased expression of the transcription factor c-Maf—normally associated with TH2 cells— and that loss of c-Maf results in a defect in IL-21 production, and consequently a defect in the maintenance of IL-23R expression and expansion of TH-17 and TFH cells. These data suggest that c-Maf induced by ICOS regulates IL-21 production that, in turn, regulates expansion of TH-17 cells and TFH cells.
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