清华大学董晨研究团队发现，共刺激分子差异性地调节ERK-Zfp831轴来塑造T滤泡辅助细胞的分化。该研究于2021年10月12日在线发表于国际一流学术期刊《免疫》。

研究人员发现12-肉豆蔻酸13-醋酸酯（PMA）+离子霉素（P+I）的刺激，在加上白细胞介素-6（IL-6），在体外有力地诱导T滤泡辅助细胞（Tfh）细胞样转录组程序。在P+I刺激下，ERK激酶途径被削弱；ERK2的抑制增强了Tfh细胞在体外和体内的发育。研究人员观察到，诱导性T细胞活化因子（ICOS），而不是CD28，缺乏激活ERK的能力，而ERK对维持Tfh细胞的发育很重要。转录因子Zfp831的表达被ERK抑制，它通过直接上调转录因子Bcl6和Tcf7的表达促进Tfh细胞分化。因此，研究人员确定了ERK-Zfp831轴，由共刺激信号调节，对Tfh细胞的发育起着关键的调节作用。

据了解，Tfh在调节体液免疫，特别是生发中心反应方面发挥着重要作用。然而，CD4⁺ T细胞如何在Tfh细胞发育过程中整合抗原和刺激信号仍不为人所知。

附：英文原文

Title: Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation

Author: Siyuan Wan, Lu Ni, Xiaohong Zhao, Xindong Liu, Wei Xu, Wei Jin, Xiaohu Wang, Chen Dong

Issue&Volume: 2021-10-12

Abstract: T follicular helper (Tfh) cells play essential roles in regulating humoral immunity,especially germinal center reactions. However, how CD4+ T cells integrate the antigenic and costimulatory signals in Tfh cell developmentis still poorly understood. Here, we found that phorbol 12-myristate 13-acetate (PMA) +ionomycin (P+I) stimulation, together with interleukin-6 (IL-6), potently induce Tfhcell-like transcriptomic programs in vitro. The ERK kinase pathway was attenuated under P+I stimulation; ERK2 inhibition enhancedTfh cell development in vitro and in vivo. We observed that inducible T cell costimulator (ICOS), but not CD28, lacked theability to activate ERK, which was important in sustaining Tfh cell development. Thetranscription factor Zfp831, whose expression was repressed by ERK, promoted Tfh celldifferentiation by directly upregulating the expression of the transcription factorsBcl6 and Tcf7. We have hence identified an ERK-Zfp831 axis, regulated by costimulation signaling,in critical regulation of Tfh cell development.

DOI: 10.1016/j.immuni.2021.09.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00403-9