HIF-1a tunes T follicular helper cell differentiation during acute viral infection

T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction and are crucial for the generation of robust antibody responses. We found that hypoxia inducible factor-1 (HIF-1a) is an inhiibitor of Tfh generation in a mouse model of acute viral infection, and that HIF-1a mediates its effects by suppressing mTORC1 activity. Bulk RNA-seq of WT or HIF-1a knockout LCMV-specific CD4 T cells, sorted into Th1, pre-Tfh, and GC Tfh populations.

滤泡辅助性T细胞（T follicular helper, Tfh）能够提供信号以启动并维持生发中心（germinal center, GC）反应，对于生成强效抗体应答具有关键作用。本研究发现，在急性病毒感染小鼠模型中，缺氧诱导因子-1α（hypoxia inducible factor-1α, HIF-1α）可作为Tfh细胞生成的抑制剂，且其通过抑制雷帕霉素靶蛋白复合物1（mTORC1）的活性来介导该调控效应。本数据集涵盖了野生型（WT）或HIF-1α敲除的淋巴细胞脉络丛脑膜炎病毒（LCMV）特异性CD4+ T细胞的批量RNA测序（bulk RNA-seq）数据，上述细胞已被分选至Th1、前滤泡辅助性T细胞（pre-Tfh）及生发中心滤泡辅助性T细胞（GC Tfh）三个亚群中。