PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis

作者：Jian-fei Cai, Yinghui Jiang, Fucai Chen, Shubin Wu, Hongjun Ren, Pingping Wang, Jiayong Wang, Wei Liu · 发表于：Immunity Inflammation and Disease · 年份：2023 · DOI：10.1002/iid3.870 · 被引用次数：19 · 研究领域：Spondyloarthritis Studies and Treatments、Psoriasis: Treatment and Pathogenesis、Rheumatoid Arthritis Research and Therapies

Abstract Objective Our previous study reveals that proprotein convertase subtilisin/kexin type 9 (PCSK9) is positively related to inflammatory markers, T helper (Th)‐17 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. Methods Serum PCSK9 was determined by enzyme‐linked immunosorbent assay in 20 AS patients and 20 healthy controls (HCs). Then naïve CD4 + T cells were isolated from AS patients and infected with PCSK9 overexpression or knockdown adenovirus followed by polarization assay. Afterward, PMA (an NF‐κB activator) was administrated. Results PCSK9 was increased in AS patients compared to HCs ( p < .001), and it was positively related to Th1 cells ( p = .050) and Th17 cells ( p = .039) in AS patients. PCSK9 overexpression increased the CD4 + IFN‐γ + cells ( p < .05), CD4 + IL‐17A + cells ( p < .01), IFN‐γ ( p < .01), and IL‐17A ( p < .01), while it exhibited no effect on CD4 + IL‐4 + cells or IL‐4 (both p > .05); its knockdown displayed the opposite function on them. Moreover, PCSK9 overexpression upregulated the p‐NF‐κB p65/NF‐κB p65 ( p < .01), while it had no effect on p‐ERK/ERK or p‐JNK/JNK (both p > .05); its knockdown decreased p‐NF‐κB p65/NF‐κB p65 ( p < .01) and p‐JNK/JNK ( p < .05). Then, PMA upregulates p‐NF‐κB p65/NF‐κB p65 ( p < .001) and increased CD4 + IFN‐γ + cells, CD4 +...