{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:20:29Z","timestamp":1787314829640,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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>\n                    Interleukin-6 (IL-6)\n                    <jats:italic>trans<\/jats:italic>\n                    -signaling modulates immune responses in asthma, yet the mechanisms linking this pathway to Th17 skewing in neutrophilic asthma remain incompletely defined. Here, we evaluated soluble gp130 (sgp130), a selective inhibitor of IL-6\n                    <jats:italic>trans<\/jats:italic>\n                    -signaling,\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . A murine neutrophilic asthma model was established by ovalbumin (OVA) sensitization followed by lipopolysaccharide (LPS) plus OVA challenge, and sgp130 was administered intratracheally. Airway neutrophilic inflammation, Th17\/Treg responses, and IL-23 expression in lung dendritic cells (DCs) were assessed, and the contribution of Th17 cells was examined by adoptive transfer. In parallel, DCs were cocultured with na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the presence of Hyper-IL-6 (an IL-6\/sIL-6R fusion protein that activates IL-6\n                    <jats:italic>trans<\/jats:italic>\n                    -signaling) with or without sgp130 to quantify DC-derived IL-23 and Th17 differentiation; additionally, DCs conditioned with Hyper-IL-6 with or without sgp130 were delivered intratracheally to establish a DC-transfer asthma model. In neutrophilic asthma, bronchoalveolar lavage fluid (BALF) levels of IL-6\/sIL-6R complex were elevated and positively associated with neutrophil counts and IL-17 production. Blockade of IL-6\n                    <jats:italic>trans<\/jats:italic>\n                    -signaling with sgp130 attenuated airway neutrophilia, reduced Th17 polarization, increased Treg response, and decreased IL-23 expression in lung DCs, whereas adoptive transfer of Th17 cells partially abrogated these protective effects. Consistently, Hyper-IL-6 increased IL-23 expression in DCs and promoted Th17 differentiation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , both of which were suppressed by sgp130. Moreover, airway transfer of Hyper-IL-6-conditioned DCs induced neutrophilic airway inflammation and Th17 polarization, while transfer of DCs conditioned with Hyper-IL-6 plus sgp130 markedly mitigated these responses. Collectively, IL-6 trans-signaling promotes Th17 polarization in neutrophilic asthma by enhancing DC IL-23 production, thereby driving neutrophilic airway inflammation, and selective inhibition with sgp130 may represent a mechanistically targeted therapeutic strategy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1787115","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:19:03Z","timestamp":1774588743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Soluble gp130 inhibits Th17 polarization in neutrophilic asthma by blocking IL-6 trans-signaling in dendritic cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Suhua","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, 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