{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:18:23Z","timestamp":1785770303597,"version":"3.56.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"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><jats:title>Background<\/jats:title><jats:p>Uncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. G\u03b1i1\/3 proteins participate in allergic inflammation by regulating immune cells. Whether G\u03b1i1\/3 proteins have a role in the development of eCRS remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the association between G\u03b1i1\/3 expression levels and CRS and the underlying mechanisms<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Western blotting and immunohistology were used to detect G\u03b1i1\/3 expression. Correlations between G\u03b1i1\/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced G\u03b1i1\/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU\/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using G\u03b1i1\/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the non-eCRS subset, the eCRS subset showed significantly increased G\u03b1i1\/3 expression levels. High nasal tissue G\u03b1i1\/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. G\u03b1i1\/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, G\u03b1i1\/3 was associated with IL-5-activated IL-5R\u03b1, promoting IL-5R\u03b1 endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after G\u03b1i1\/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in G\u03b1i1\/3-double-knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased G\u03b1i1\/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. G\u03b1i1\/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1460104","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:29:35Z","timestamp":1736227775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["G\u03b1i1\/3 signaling mediates IL-5-induced eosinophil activation and type 2 inflammation in eosinophilic chronic 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