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Immunol."],"abstract":"<jats:p>Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%\u20132% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response <jats:italic>via<\/jats:italic> their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2\/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3\/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-\u03baB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation <jats:italic>via<\/jats:italic> decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.<\/jats:p>","DOI":"10.3389\/fimmu.2021.591706","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T05:33:11Z","timestamp":1614231191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Down-Regulation of LOC645166 in T Cells of Ankylosing Spondylitis Patients Promotes the NF-\u03baB Signaling via Decreasingly Blocking Recruitment of the IKK Complex to K63-Linked Polyubiquitin 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