Sex and disease regulate major histocompatibility complex class I expression in human lung epithelial cells.

Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE

Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-

Histocompatibility Antigens Class I*/metabolism ; Histocompatibility Antigens Class I*/genetics ; Lung*/metabolism ; Lung*/cytology ; Lung*/immunology ; Epithelial Cells*/metabolism; Humans ; Female ; Male ; Sex Characteristics ; Lung Diseases/metabolism

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T-cells for immunosurveillance of infection and cancer. Recent studies indicate lineage-specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single-cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady-state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease.
(© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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FDN-148400 Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)

Keywords: MHC I; antigen presentation; chronic respiratory diseases; lung epithelial cells; sexual dimorphism

0 (Histocompatibility Antigens Class I)

Date Created: 20240902 Date Completed: 20240902 Latest Revision: 20240906

20240906

PMC11368564

10.14814/phy2.70025

39223101