{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:31:36Z","timestamp":1792690296804,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"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:p>Fatal influenza (flu) virus infection often activates excessive inflammatory signals, leading to multi-organ failure and death, also referred to as cytokine storm. PPAR\u03b3 (Peroxisome proliferator-activated receptor gamma) agonists are well-known candidates for cytokine storm modulation. The present study identified that influenza infection reduced PPAR\u03b3 expression and decreased PPAR\u03b3 transcription activity in human alveolar macrophages (AMs) from different donors. Treatment with PPAR\u03b3 agonist Troglitazone ameliorated virus-induced proinflammatory cytokine secretion but did not interfere with the IFN-induced antiviral pathway in human AMs. In contrast, PPAR\u03b3 antagonist and knockdown of PPAR\u03b3 in human AMs further enhanced virus-stimulated proinflammatory response. In a mouse model of influenza infection, flu virus dose-dependently reduced PPAR\u03b3 transcriptional activity and decreased expression of PPAR\u03b3. Moreover, PPAR\u03b3 agonist troglitazone significantly reduced high doses of influenza infection-induced lung pathology. In addition, flu infection reduced PPAR\u03b3 expression in all mouse macrophages, including AMs, interstitial macrophages, and bone-marrow-derived macrophages but not in alveolar epithelial cells. Our results indicate that the influenza virus specifically targets the PPAR\u03b3 pathway in macrophages to cause acute injury to the lung.<\/jats:p>","DOI":"10.3389\/fimmu.2022.958801","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T06:48:51Z","timestamp":1661410131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Influenza virus causes lung immunopathology through down-regulating PPAR\u03b3 activity in 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