Regulation of MHC I expression in lung epithelial cells during inflammation.

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Infections of the respiratory tract are a perennial cause of death worldwide. These diseases typically affect the lung epithelium, composed of three main types of cells: alveolar type I (AT1), alveolar type 2 (AT2), and bronchiolar cells. These three epithelial cells (ECs) types express constitutively low levels of MHC I, representing less than 1% of the levels found in thymic ECs. This weak expression is surprising since it could disturb the elimination of infected or transformed cells. We hypothesized that lung ECs should be able to upregulate their MHC I expression swiftly when needed. We induced lung inflammation in mice using inhalation of LPS. We observed that AT1, AT2, and bronchiolar cells upregulated by 25 times their surface expression of MHC I during LPS-induced inflammation. The concerted production of the three IFN families, thanks to the factors Stat1, Stat2, and Nlrc5, drove this upregulation. The low expression of genes involved in the peptide loading of MHC I molecules nevertheless hampered MHC I upregulation in lung ECs. Discrete gene subsets were selectively differentially regulated by interferon signaling in each type of lung ECs. AT1 increased genes related to cytokine-mediated signaling pathway while AT2 and bronchiolar decreased genes involved in their specialized functions, essential to maintaining the integrity of lung epithelium (epithelium regeneration and cilium movement, respectively). Our results showed a balance between the expression of transcripts involved in immune defenses and transcripts maintaining lung epithelium integrity in lung ECs. It paves the way to a better understanding of antigen presentation in lung ECs, and the pathogenesis of lung inflammation.