Disease-specific expansion of CD29+IL-17RA+ T effector cells possessing multiple signalling pathways in spondyloarthritis
Disease-specific expansion of CD29+IL-17RA+ T effector cells possessing multiple signalling pathways in spondyloarthritis
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脊柱关节炎中具有多种信号通路的 CD29 IL-17RA T 效应细胞的疾病特异性扩增
DOI：
10.1093/rheumatology/keac391
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发表时间：
2022
期刊：
影响因子：
5.5
通讯作者：
Kaneko Yuko
中科院分区：
文献类型：
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作者：
Akiyama Mitsuhiro;Yoshimoto Keiko;Ishigaki Sho;Suzuki Katsuya;Takeuchi Tsutomu;Kaneko Yuko
目的细胞通过整合素粘附于内植纤维软骨，并需要il - 17ra介导的信号来维持其效应功能。我们分析了SpA患者炎症病变和外周血中的CD29+IL-17RA+T细胞，并研究了它们与疾病活动性和治疗反应的关系。方法使用公开的大细胞RNA测序数据对PsA滑膜液T细胞进行转录组分析。健康对照（n= 37）、RA （n= 12）、igg4相关疾病（IgG4-RD;n= 12）、大血管炎（LVV;n= 12）和SpA （n= 28）采集血样，采用流式细胞术进行分析。结果炎性关节炎关节的st细胞表达CD29和IL-17RA。CD29+IL-17RA+T细胞显示CXCR3+CD45RA+效应细胞富集，脾酪氨酸激酶（Syk）、核因子κB （NF-κB）和Janus激酶信号转导和转录激活因子（JAK-STAT）通路活化。SpA患者外周血CD29+IL-17RA+T细胞比例与RA、IgG4-RD或LVV患者及健康对照组相比显著升高。根据ASDAS-CRP评分，treatment-naïve SpA活动性患者的CD29+IL-17RA+T细胞比例与疾病活动性呈正相关。抗il -17单克隆抗体降低CD29+IL-17RA+T细胞，而抗tnf单克隆抗体不降低。结论scd29 +IL-17RA+ Syk、NF-κB和JAK-STAT通路增强的T效应细胞在SpA中特异性增加，并与疾病活动性相关，暗示这一新发现的T细胞群在发病机制中起作用。抗il -17单克隆抗体可能通过减少这种致病性T细胞群对患者有效。
ObjectivesT cells adhere to enthesis fibrocartilage via integrins and intrinsically require IL-17RA-mediated signals to maintain their effector function. We analysed CD29+IL-17RA+T cells in inflamed lesions and peripheral blood in patients with SpA and investigated their association with disease activity and therapeutic response.MethodsTranscriptome analysis of synovial fluid T cells from PsA was performed using publicly available bulk cell RNA sequencing data. Blood samples were obtained from healthy controls (n= 37), RA (n= 12), IgG4-related disease (IgG4-RD;n= 12), large vessel vasculitis (LVV;n= 12) and SpA (n= 28) and were analysed by flow cytometry.ResultsT cells in the inflamed joints of PsA showed CD29 and IL-17RA expression. CD29+IL-17RA+T cells showed enriched CXCR3+CD45RA+effector cells and activation of spleen tyrosine kinase (Syk), nuclear factor κB (NF-κB) and Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathways. The proportion of peripheral blood CD29+IL-17RA+T cells was significantly increased in patients with SpA compared with patients with RA, IgG4-RD or LVV and in healthy controls. Based on the ASDAS-CRP scores, the proportion of CD29+IL-17RA+T cells was positively correlated with disease activity in treatment-naïve patients with active SpA. Anti-IL-17 but not anti-TNF monoclonal antibodies reduced CD29+IL-17RA+T cells.ConclusionsCD29+IL-17RA+T effector cells with enhanced Syk, NF-κB and JAK-STAT pathways were specifically increased in SpA and were correlated with disease activity, implicating a role of this newly identified T cell population in the pathogenesis. Anti-IL-17 monoclonal antibodies may be effective for patients by reducing this pathogenic T cell population.