IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection.
IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection.
复制标题
在慢性病毒感染过程中，IL-6和IL-27在调节CD4T细胞反应中扮演着不同的和多余的角色。
DOI：
10.3389/fimmu.2023.1221562
复制
发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
IL-6细胞因子家族通过共同的信号转导分子gp130与细胞因子特异性受体结合来传递信号。CD4 T细胞上的Gp130信号在控制淋巴细胞性脉络丛脑膜炎病毒克隆13 （LCMV Cl13）小鼠的慢性感染中至关重要，但IL-6细胞因子家族单个成员的确切作用尚不完全清楚。转录分析强调了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T滤泡辅助细胞（Tfh）分化和IL-21产生相关的基因。此外，Il27r−/−Il6ra−/−小鼠不能产生抗体或CD8 t细胞免疫，也不能控制LCMV Cl13。Il27r−/−Il6ra−/−Tfh细胞的转录组学和表型分析显示，IL-6R和IL-27R信号是激活CD4 T细胞内关键通路所必需的。IL-6和IL-27信号传导具有不同且重叠的作用，IL-6调节Tfh分化，IL-27调节CD4 T细胞存活，两者均冗余促进IL-21。
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, Il27r−/−Il6ra−/− mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r−/−Il6ra−/− 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.