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The lung epithelium comprises three main cell types: alveolar type I (AT1), alveolar type II (AT2), and bronchiolar cells. Constitutively, these three cell types express extremely low amounts of surface MHC class I (MHC I) molecules, that is, &amp;lt;1% of levels found on medullary thymic epithelial cells (ECs). We report that inhalation of the TLR4 ligand LPS upregulates cell surface MHC I by \u223c25-fold on the three subtypes of mouse lung ECs. This upregulation is dependent on Nlrc5, Stat1, and Stat2 and caused by a concerted production of the three IFN families. It is nevertheless hampered, particularly in AT1 cells, by the limited expression of genes instrumental in the peptide loading of MHC I molecules. Genes involved in production and response to cytokines and chemokines were selectively induced in AT1 cells. However, discrete gene subsets were selectively downregulated in AT2 or bronchiolar cells following LPS inhalation. Genes downregulated in AT2 cells were linked to cell differentiation and cell proliferation, and those repressed in bronchiolar cells were primarily involved in cilium function. Our study shows a delicate balance between the expression of transcripts maintaining lung epithelium integrity and transcripts involved in Ag presentation in primary lung ECs.<\/jats:p>","DOI":"10.4049\/jimmunol.2100664","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T18:21:09Z","timestamp":1645035669000},"page":"1021-1033","source":"Crossref","is-referenced-by-count":14,"title":["Regulation of MHC Class I Expression in Lung Epithelial Cells during Inflammation"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-1148","authenticated-orcid":false,"given":"Justine","family":"Math\u00e9","sequence":"first","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-7734","authenticated-orcid":false,"given":"Mohamed","family":"Benhammadi","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi S","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center , College Station, TX"},{"name":"Department of Immunology, Hokkaido University Graduate School of Medicine , Sapporo, Hokkaido,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-0936","authenticated-orcid":false,"given":"Sylvie","family":"Brochu","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-7383","authenticated-orcid":false,"given":"Claude","family":"Perreault","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"2025021008560791700_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2014.10.012","article-title":"The nature of self for T cells\u2014a systems-level perspective","volume":"34","author":"Granados","year":"2015","journal-title":"Curr. 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