{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:12:33Z","timestamp":1787613153760,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Asthma is a heterogeneous disease characterized by airway inflammation and hyperresponsiveness (AHR). Ozone, a common air pollutant, induces a neutrophilic phenotype of asthma that is resistant to corticosteroids. Osteopontin has been implicated in airway inflammation, but its role in ozone-induced pulmonary responses remains unclear. We hypothesized that osteopontin contributes to neutrophilic airway inflammation and AHR through dendritic cell (DC)\u2013neutrophil interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male BALB\/c mice were exposed to ozone (2 ppm, 3 hours) or ambient air. AHR and bronchoalveolar lavage fluid (BALF) cell counts were assessed, and osteopontin levels were measured. Single-cell RNA sequencing of lung tissue was performed to identify osteopontin-producing cells and infer cell\u2013cell communication using CellChat analysis. Functional validation included administration of clodronate liposomes to affect monocyte-derived DCs and an anti-osteopontin neutralizing antibody. In addition, RNA sequencing of bone marrow-derived neutrophils stimulated with osteopontin\n                      <jats:italic>in vitro<\/jats:italic>\n                      was conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ozone exposure significantly increased neutrophils in BALF, enhanced AHR, and elevated osteopontin levels in lung tissue. Single-cell RNA sequencing showed DCs, particularly monocyte-derived DCs, as the main source of osteopontin, with downstream signaling to macrophages, fibroblasts, pericytes, smooth muscle cells, and neutrophils. Clodronate liposome treatment reduced osteopontin expression and attenuated ozone-induced neutrophilic inflammation and AHR. Neutralization of osteopontin suppressed neutrophilic airway inflammation but did not significantly improve AHR.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , osteopontin stimulation of neutrophils upregulated\n                      <jats:italic>NDUFA1<\/jats:italic>\n                      , a mitochondrial complex I gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present findings indicate that ozone exposure induces osteopontin production primarily from monocyte-derived DCs, which promotes neutrophilic airway inflammation through DC\u2013neutrophil interactions, while having a limited impact on airway hyperresponsiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1748667","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:18:04Z","timestamp":1773911884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteopontin from monocyte-derived dendritic cells mediates ozone-induced pulmonary responses in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Hiroki","family":"Tashiro","sequence":"first","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kuwahara","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Konomi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takamori","sequence":"additional","affiliation":[{"name":"Clinical Research Center in Hiroshima, Hiroshima University Hospital","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Hospital","place":["Saga, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4S","DOI":"10.1378\/chest.10-0100","article-title":"The relationship of airway hyperresponsiveness and airway inflammation: Airway hyperresponsiveness in asthma: Its measurement and clinical significance","volume":"138","author":"Busse","year":"2010","journal-title":"Chest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0288TR","article-title":"The gut microbiome and ozone-induced airway hyperresponsiveness. 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