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

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-as...

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Published inNature communications Vol. 13; no. 1; p. 5866
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 04.10.2022
Nature Publishing Group UK
Nature Portfolio
Subjects
AKT protein
Autoimmune diseases
CD4 antigen
Cell differentiation
Differentiation (biology)
Experimental autoimmune uveitis
Experimental autoimmune uveoretinitis
Forkhead protein
FOXO1 protein
Gene regulation
Gene sequencing
Helper cells
Inflammatory diseases
Kinases
Lymphocytes
Lymphocytes T
Pathogenicity
Pathogens
Plasma cells
Therapeutic applications
Therapeutic targets
Uveitis
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33502-7