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

Zihao Liu; He Xie; Ling Li; Dan Jiang; Yuna Qian; Xinhao Zhu; Mali Dai; Yanxiao Li; Ruifen Wei; Zan Luo; Weihao Xu; Qinxiang Zheng; Jianliang Shen; Meng Zhou; Wenwen Zeng; Wei Chen

doi:10.1016/j.mucimm.2023.11.008

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

Mucosal Immunol. 2023 Nov 24:S1933-0219(23)00091-0. doi: 10.1016/j.mucimm.2023.11.008. Online ahead of print.

Authors

Zihao Liu¹, He Xie¹, Ling Li², Dan Jiang¹, Yuna Qian³, Xinhao Zhu¹, Mali Dai¹, Yanxiao Li¹, Ruifen Wei¹, Zan Luo¹, Weihao Xu¹, Qinxiang Zheng¹, Jianliang Shen⁴, Meng Zhou¹, Wenwen Zeng⁵, Wei Chen⁶

Affiliations

¹ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
² National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China; The Affiliated Ningbo Eye Hospital of Wenzhou Medical University, Ningbo, Zhejiang, China.
³ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
⁴ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
⁵ Institute for Immunology, School of Medicine, and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. Electronic address: wenwenzeng@tsinghua.edu.cn.
⁶ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: chenweimd@wmu.edu.cn.

PMID: 38007004
DOI: 10.1016/j.mucimm.2023.11.008

Abstract

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.