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In the current study, we investigated the response of T cells to hyperosmotic stress in the bony fish Nile tilapia (Oreochromis niloticus). As a euryhaline fish, tilapia was able to adapt to a wide range of salinities; however, hypertonic stress caused inflammation and excessive T-cell activation. Furthermore, hypertonic stress increased the expression of IL-17A in T cells, upregulated the transcription factor ROR\u03b1, and activated STAT3 signaling, along with IL-6\u2013 and TGF-\u03b21\u2013mediated pathways, revealing an enhanced Th17 response in this early vertebrate. These hypertonic stress\u2013induced events collectively resulted in an impaired antibacterial immune response in tilapia. Hypertonic stress elevated the intracellular ROS level, which in turn activated the p38\u2013MK2 signaling pathway to promote IL-17A production by T cells. Both ROS elimination and the p38\u2013MK2 axis blockade diminished the increased IL-17A production in T cells under hypertonic conditions. Moreover, the produced proinflammatory cytokines further amplified the hypertonic stress signaling via the MKK6\u2013p38\u2013MK2 axis\u2013mediated positive feedback loop. To our knowledge, these findings represent the first description of the mechanism by which T-cell immunity responds to hypertonic stress in early vertebrates, thus providing a novel perspective for understanding the adaptive evolution of T cells under environmental stress.<\/jats:p>","DOI":"10.4049\/jimmunol.2300251","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T09:27:03Z","timestamp":1714728423000},"page":"1877-1890","source":"Crossref","is-referenced-by-count":15,"title":["Hyperosmotic Stress Induces Inflammation and Excessive Th17 Response to Blunt T-Cell Immunity in Tilapia"],"prefix":"10.1093","volume":"212","author":[{"given":"Jiansong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhuo","family":"Rao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Jiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyou","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-6341","authenticated-orcid":false,"given":"Ding","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-5012","authenticated-orcid":false,"given":"Jialong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai ,","place":["China"]},{"name":"Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center , Qingdao ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"2025020405512418700_r1","doi-asserted-by":"crossref","first-page":"143718","DOI":"10.1016\/j.scitotenv.2020.143718","article-title":"Epidemiological and animal evidence for the role of air pollution in intestinal diseases","volume":"757","author":"Vignal","year":"2021","journal-title":"Sci. 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