Runx3 drives a tissue-residency program that is absent in CD4+ T cells [RNA-seq]

Pattens of tissue-residency differs between CD4+ and CD8+ memory T cells in evironmentally exposed organs. The lineage-controlling transcription factor Runx3, expressed in CD8+ T cells, is responsible for shaping a tissue-resident gene network in response to the cytokine TGF-b. While the lack of Runx3 by CD4+ T cells precludes these transcriptional changes, Runx3-overexpression in CD+ T cells enable phenotypical, transcriptional and functional changes to allow residency. Overall design: Effector CD4+ and CD8+ T cells were transduced with Control and Runx3-expressing retrovirus. Cells were co-transferred to HSV infected mice and isolated from the skin for RNA sequencing 14 days post HSV infection.环境暴露器官中，CD4+与CD8+记忆T细胞的组织驻留模式存在显著差异。在CD8+ T细胞中表达的谱系调控转录因子Runx3，可响应细胞因子转化生长因子-β（transforming growth factor-β，TGF-β），调控构建组织驻留相关基因网络。CD4+ T细胞因缺乏Runx3，无法发生此类转录调控改变；但若在CD4+ T细胞中过表达Runx3，则可使其获得表型、转录及功能层面的特征性改变，从而具备组织驻留能力。实验设计概述：将效应性CD4+与CD8+ T细胞分别用空载对照逆转录病毒及表达Runx3的逆转录病毒进行转导，随后将转导后的细胞共输注至单纯疱疹病毒（Herpes Simplex Virus，HSV）感染的小鼠体内，并于HSV感染后14天从皮肤组织中分离细胞，开展RNA测序（RNA sequencing）。