{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:11:16Z","timestamp":1792008676619,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our previous study reveals that proprotein convertase subtilisin\/kexin type 9 (PCSK9) is positively related to inflammatory markers, T helper (Th)\u201017 cells, and treatment response in ankylosing spondylitis (AS) patients. Subsequently, this study aimed to explore the effect of PCSK9 on Th cell differentiation and its potential molecular mechanism in AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum PCSK9 was determined by enzyme\u2010linked immunosorbent assay in 20 AS patients and 20 healthy controls (HCs). Then na\u00efve CD4<jats:sup>+<\/jats:sup> T cells were isolated from AS patients and infected with PCSK9 overexpression or knockdown adenovirus followed by polarization assay. Afterward, PMA (an NF\u2010\u03baB activator) was administrated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PCSK9 was increased in AS patients compared to HCs (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), and it was positively related to Th1 cells (<jats:italic>p<\/jats:italic>\u2009=\u2009.050) and Th17 cells (<jats:italic>p<\/jats:italic>\u2009=\u2009.039) in AS patients. PCSK9 overexpression increased the CD4<jats:sup>+<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup> cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05), CD4<jats:sup>+<\/jats:sup>IL\u201017A<jats:sup>+<\/jats:sup> cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), IFN\u2010\u03b3 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), and IL\u201017A (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), while it exhibited no effect on CD4<jats:sup>+<\/jats:sup>IL\u20104<jats:sup>+<\/jats:sup>cells or IL\u20104 (both <jats:italic>p<\/jats:italic>\u2009&gt;\u2009.05); its knockdown displayed the opposite function on them. Moreover, PCSK9 overexpression upregulated the p\u2010NF\u2010\u03baB p65\/NF\u2010\u03baB p65 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), while it had no effect on p\u2010ERK\/ERK or p\u2010JNK\/JNK (both <jats:italic>p<\/jats:italic>\u2009&gt;\u2009.05); its knockdown decreased p\u2010NF\u2010\u03baB p65\/NF\u2010\u03baB p65 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) and p\u2010JNK\/JNK (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Then, PMA upregulates p\u2010NF\u2010\u03baB p65\/NF\u2010\u03baB p65 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and increased CD4<jats:sup>+<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup> cells, CD4<jats:sup>+<\/jats:sup>IL\u201017A<jats:sup>+<\/jats:sup> cells, IFN\u2010\u03b3, and IL\u201017A (all <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), also it alleviated the effect of PCSK9 knockdown on NF\u2010\u03baB inhibition and Th cell differentiation (all <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PCSK9 enhances Th1 and Th17 cell differentiation in an NF\u2010\u03baB\u2010dependent manner in AS, while further validation is necessary.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.870","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T11:30:30Z","timestamp":1685100630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor\u2010\u03baB pathway in ankylosing spondylitis"],"prefix":"10.1002","volume":"11","author":[{"given":"Jianfei","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Huadong Hospital Affiliated with Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Pharmacy China Pharmaceutical University Nanjing 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