IL-33 from oligodendrocytes sustains effector differentiation of CD8+ tissue-resident T cells and is a druggable target in CNS autoimmune disease

Our study identifies oligodendrocyte-derived IL-33 as a druggable tissue factor regulating the differentiation and survival of self-reactive CD8+ T cell in the inflamed CNS. This finding introduces tissue factors as a novel category of immune targets for treating chronic CNS autoimmune diseases. Transcriptional activity of FACS-sorted brain CD8 GP33-41+ T cells from WT, MOG-GP, and IL-33 cKO MOG-GP mice at 21 days after rLCMV-GP33 infection. Transcriptional activity using scRNAseq of FACS-sorted brain CD45+ cells from MOG-GP, and IL-33 cKO MOG-GP mice at 21 days after rLCMV-GP33 infectionfon.

本研究证实，少突胶质细胞来源的IL-33是一种可成药组织因子，可调控炎症性中枢神经系统（Central Nervous System, CNS）内自身反应性CD8阳性T细胞的分化与存活。该发现将组织因子确立为治疗慢性中枢神经系统自身免疫性疾病的新型免疫靶点类别。本数据集包含野生型（Wild Type, WT）、MOG-GP以及IL-33条件性敲除（conditional knockout, cKO）MOG-GP小鼠在重组淋巴细胞脉络丛脑膜炎病毒-GP33（recombinant Lymphocytic Choriomeningitis Virus-GP33, rLCMV-GP33）感染后第21天时，经荧光激活细胞分选（Fluorescence-Activated Cell Sorting, FACS）纯化的脑组织CD8 GP33-41阳性T细胞的转录活性数据。本数据集还包含MOG-GP与IL-33条件性敲除MOG-GP小鼠在重组淋巴细胞脉络丛脑膜炎病毒-GP33感染后第21天时，经荧光激活细胞分选纯化的脑组织CD45阳性细胞的单细胞RNA测序（single-cell RNA sequencing, scRNAseq）转录活性数据。