{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:30:14Z","timestamp":1792870214750,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["RO1-HL150587"],"award-info":[{"award-number":["RO1-HL150587"]}],"id":[{"id":"10.13039\/100000050","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>Introduction<\/jats:title>\n                    <jats:p>Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-\u03b3, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      . To determine whether CD8 T cells and their released cytokine IFN-\u03b3 are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-\u03b3 monoclonal antibody (mAb) treatment\n                      <jats:italic>in vivo<\/jats:italic>\n                      . We assessed the effects of CD8 T cells and cytokine IFN-\u03b3 on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      . Depletion of CD8 T cells or neutralization of cytokine IFN-\u03b3 using anti-CD8 or anti-IFN-\u03b3 monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-\u03b3 with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-\u03b3 signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our data demonstrate that CD8 T-cell response and cytokine IFN-\u03b3 are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1268078","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T19:24:40Z","timestamp":1698348280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["CD8 T cell response and its released cytokine IFN-\u03b3 are necessary for lung alveolar epithelial repair during bacterial pneumonia"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiaoying","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan Alexandra","family":"Pantuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Ru","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Bahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kosmider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single-cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.devcel.2021.11.007","article-title":"NHLBI LungMAP Consortium. 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