A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development.
A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development.
复制标题
DOI：
10.1016/j.bbrc.2023.04.065
复制
发表时间：
2023-04
影响因子：
3.1
通讯作者：
Kazuma Iida;K. Suga;Kotaro Suzuki;Shunjiro Kurihara;Yoko Yabe;T. Kageyama;K. Meguro;S. Tanaka;A. Iwata;A. Suto;Hiroshi Nakajima
中科院分区：
文献类型：
--
作者：
Kazuma Iida;K. Suga;Kotaro Suzuki;Shunjiro Kurihara;Yoko Yabe;T. Kageyama;K. Meguro;S. Tanaka;A. Iwata;A. Suto;Hiroshi Nakajima
滤泡调节性T（Tfr）细胞是CD 4 + Foxp 3+调节性T（Treg）细胞的一个亚群，位于淋巴滤泡和生发中心（GC），调节抗体应答。Tfr细胞表达滤泡辅助T（Tfh）细胞的功能分子，包括CXCR 5和Bcl 6。CD 25 −成熟Tfr细胞通过CD 25+未成熟Tfr细胞从CD 25 +Treg细胞分化而来。其他人和我们已经表明，Achaete-scute复合物同系物2（Ascl 2）在Tfh细胞发育中起作用;然而，Ascl 2在Tfr细胞发育中的作用仍不清楚。在此，我们发现Ascl 2在CD 25 +Tfr细胞和CD 25 −Tfr细胞中高度优先表达，并且从CD 25 +Tfr细胞向CD 25 − Tfr细胞的分化因Ascl 2的缺失而受损。此外，Treg细胞中Ascl 2的强制表达下调了CD 25的表达，并抑制了IL-2诱导的STAT 5磷酸化，这是已知的抑制CD 25 −Tfr细胞发育。最后，我们发现Treg细胞中Ascl 2对CD 25的下调不依赖于Bach 2，Bach 2也调节CD 25 +Tfr细胞中的CD 25下调。这些结果表明，Ascl 2在Tfr细胞的发育中起着至关重要的作用，可能是通过在Bach 2非依赖性机制中下调CD 25表达。
T follicular regulatory (Tfr) cells, a subset of CD4+Foxp3+regulatory T (Treg) cells, locate to the lymphoid follicle and germinal center (GC) and regulate antibody responses. Tfr cells express the functional molecules of follicular helper T (Tfh) cells, including CXCR5 and Bcl6. CD25−mature Tfr cells differentiate from CD25+Treg cells through CD25+immature Tfr cells. Others and we have shown that Achaete-scute complex homolog 2 (Ascl2) plays a role in Tfh cell development; however, the role of Ascl2 in the development of Tfr cells remains unclear. Here, we found that Ascl2 was highly and preferentially expressed in CD25+Tfr cells and CD25−Tfr cells, and that the differentiation from CD25+Tfr cells to CD25−Tfr cells was impaired by the absence of Ascl2. Furthermore, the forced Ascl2 expression in Treg cells downregulated CD25 expression and suppressed IL-2-induced phosphorylation of STAT5, which is known to suppress CD25−Tfr cell development. Finally, we found that the downregulation of CD25 by Ascl2 in Treg cells is independent of Bach2, which also regulates CD25 downregulation in CD25+Tfr cells. These results suggest that Ascl2 plays a vital role in developing Tfr cells, possibly by downregulating CD25 expression in a Bach2-independent mechanism.