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

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...

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Detalles Bibliográficos
Autores principales: Li, He, Xie, Lihui, Zhu, Lei, Li, Zhaohuai, Wang, Rong, Liu, Xiuxing, Huang, Zhaohao, Chen, Binyao, Gao, Yuehan, Wei, Lai, He, Chang, Ju, Rong, Liu, Yizhi, Liu, Xialin, Zheng, Yingfeng, Su, Wenru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532430/
https://www.ncbi.nlm.nih.gov/pubmed/36195600
http://dx.doi.org/10.1038/s41467-022-33502-7
Descripción
Sumario: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.