Division of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United States.
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Front Immunol. 2023 Jul 31;14:1221562. doi: 10.3389/fimmu.2023.1221562. eCollection 2023.
The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21.
白细胞介素 6（IL-6）细胞因子家族通过与细胞因子特异性受体结合的共同信号转导分子 gp130 进行信号传递。gp130 在 CD4 T 细胞上的信号传导对于控制小鼠淋巴细胞性脉络丛脑膜炎病毒克隆 13（LCMV Cl13）的慢性感染至关重要，但 IL-6 细胞因子家族的各个成员的确切作用尚不完全清楚。转录分析突出了 gp130 信号在 LCMV Cl13 感染后促进 CD4 T 细胞关键过程中的重要性，特别是与滤泡辅助性 T（Tfh）细胞分化和白细胞介素 21（IL-21）产生相关的基因。此外，IL-6R 和 IL-27R 信号缺失的小鼠无法产生抗体或 CD8 T 细胞免疫，也无法控制 LCMV Cl13。Tfh 细胞的转录组学和表型分析表明，IL-6R 和 IL-27R 信号需要激活 CD4 T 细胞内的关键途径。IL-6 和 IL-27 信号具有独特且重叠的作用，IL-6 调节 Tfh 分化，IL-27 调节 CD4 T 细胞存活，两者都可冗余地促进 IL-21。
