Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development

• Published in: Mucosal immunology Vol. 17; no. 3; pp. 491 - 507
• Main Authors: Liu, Zihao, Xie, He, Li, Ling, Jiang, Dan, Qian, Yuna, Zhu, Xinhao, Dai, Mali, Li, Yanxiao, Wei, Ruifen, Luo, Zan, Xu, Weihao, Zheng, Qinxiang, Shen, Jianliang, Zhou, Meng, Zeng, Wenwen, Chen, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Animals; Cellular Microenvironment; Conjunctiva - immunology; Conjunctiva - pathology; Disease Models, Animal; Dry Eye Syndromes - etiology; Dry Eye Syndromes - immunology; Epithelial Cells - immunology; Gene Expression Profiling; Humans; Inflammation - immunology; Macrophages - immunology; Mice; Mice, Inbred C57BL; Single-Cell Analysis; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transcriptome
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1016/j.mucimm.2023.11.008

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.