PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis
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 PCSK...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.870 |
| _version_ | 1797816624146808832 |
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| author | Jianfei Cai Yinghui Jiang Fucai Chen Shubin Wu Hongjun Ren Pingping Wang Jiayong Wang Wei Liu |
| author_facet | Jianfei Cai Yinghui Jiang Fucai Chen Shubin Wu Hongjun Ren Pingping Wang Jiayong Wang Wei Liu |
| author_sort | Jianfei Cai |
| collection | DOAJ |
| description | 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+IL‐17A+ cells, IFN‐γ, and IL‐17A (all p < .01), also it alleviated the effect of PCSK9 knockdown on NF‐κB inhibition and Th cell differentiation (all p < .01). Conclusion PCSK9 enhances Th1 and Th17 cell differentiation in an NF‐κB‐dependent manner in AS, while further validation is necessary. |
| first_indexed | 2024-03-13T08:40:24Z |
| format | Article |
| id | doaj.art-c0cd96e476444ea89263576161727e0b |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-13T08:40:24Z |
| publishDate | 2023-05-01 |
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| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-c0cd96e476444ea89263576161727e0b2023-05-30T12:34:31ZengWileyImmunity, Inflammation and Disease2050-45272023-05-01115n/an/a10.1002/iid3.870PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitisJianfei Cai0Yinghui Jiang1Fucai Chen2Shubin Wu3Hongjun Ren4Pingping Wang5Jiayong Wang6Wei Liu7Department of Rheumatology and Immunology Huadong Hospital Affiliated with Fudan University Shanghai ChinaDepartment of Traditional Chinese Medicine and Pharmacy China Pharmaceutical University Nanjing ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaDepartment of Rheumatology and Immunology Shanghai Qiang‐zhi Hospital Shanghai ChinaAbstract 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+IL‐17A+ cells, IFN‐γ, and IL‐17A (all p < .01), also it alleviated the effect of PCSK9 knockdown on NF‐κB inhibition and Th cell differentiation (all p < .01). Conclusion PCSK9 enhances Th1 and Th17 cell differentiation in an NF‐κB‐dependent manner in AS, while further validation is necessary.https://doi.org/10.1002/iid3.870ankylosing spondylitisnuclear factor‐κB pathwayproprotein convertase subtilisin/kexin type 9T helper 1 cellsT helper 17 cells |
| spellingShingle | Jianfei Cai Yinghui Jiang Fucai Chen Shubin Wu Hongjun Ren Pingping Wang Jiayong Wang Wei Liu PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis Immunity, Inflammation and Disease ankylosing spondylitis nuclear factor‐κB pathway proprotein convertase subtilisin/kexin type 9 T helper 1 cells T helper 17 cells |
| title | PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis |
| title_full | PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis |
| title_fullStr | PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis |
| title_full_unstemmed | PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis |
| title_short | PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis |
| title_sort | pcsk9 promotes t helper 1 and t helper 17 cell differentiation by activating the nuclear factor κb pathway in ankylosing spondylitis |
| topic | ankylosing spondylitis nuclear factor‐κB pathway proprotein convertase subtilisin/kexin type 9 T helper 1 cells T helper 17 cells |
| url | https://doi.org/10.1002/iid3.870 |
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