Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis

作者：He Li, Lihui Xie, Lei Zhu, Zhaohuai Li, Rong Wang, Xiuxing Liu, Xiuxing Liu, Zhaohao Huang, Binyao Chen, Yuehan Gao, Lai Wei, Chang He, Rong Ju, Yizhi Liu, Xialin Liu, Xialin Liu, Yingfeng Zheng, Wenru Su · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-33502-7 · 被引用次数：61 · 研究领域：Cancer Mechanisms and Therapy、Ocular Diseases and Behçet’s Syndrome、interferon and immune responses

Abstract Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4 + T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4 + T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.