{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:54:55Z","timestamp":1776318895855,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>HIV infection is risk factor for a wide spectrum of pulmonary diseases, with incidence rates significantly higher in people living with HIV (PLWH). Despite antiretroviral therapy, persistent immune activation and recurrent injury continue to compromise lung integrity in this population. However, the mechanism by which HIV disrupts alveolar homeostasis and affects epithelial, immune, and stromal compartments in the lungs remain undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the cellular and molecular landscape of HIV infection within the lungs, the focus of the study was to assess epithelial remodeling and HIV-driven alterations in lung cellular composition and transcriptional programs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single cell RNA sequencing (scRNA-seq) was performed on human lung tissues obtained from HIV infected and uninfected individuals, including both non-smokers and smokers. A total of 54,230 cells across all experimental groups were analyzed using integration and Uniform Manifold Approximation and Projection (UMAP) clustering to identify transcriptionally distinct cell populations and HIV-associated changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HIV infection profoundly altered lung cellular composition marked by expansion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      , CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells, B cells, and non-classical monocytes, alongside reduced fibroblast abundance. Alveolar Type I and Type II cells displayed robust HIV-associated transcriptional reprogramming. Fibroblast and smooth muscle cells showed enhanced proinflammatory and stress responsiveness affecting extracellular matrix and contractile programs. EMT marker analysis revealed cell type specific shifts with: (a) AT1 cells exhibiting reduced\n                      <jats:italic>CDH1<\/jats:italic>\n                      and increased vimentin gene expression, (b) AT2 cells adopting a hybrid epithelial mesenchymal phenotype, and (c) myofibroblast cluster displaying amplified mesenchymal activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings revealed HIV as a potential driver of epithelial dysregulation and airway remodeling in the human lungs. These observations provide a framework for future studies aimed at determining whether modulation of these pathways may have therapeutic relevance, particularly in the context of lung pathology in PLWH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1789140","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:24:55Z","timestamp":1776317095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["scRNA sequencing revealed HIV-associated inflammation-mediated lung epithelial dysregulation and fibroblast remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Khursheed Ul","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester Medical Center","place":["Rochester, NY, United 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