广州玻璃贴膜价格联盟

粘膜免疫相关恒定T细胞参与强直性脊柱炎的发病

中国风湿病公众论坛2019-09-23 14:08:12

作者:Gracey E, et al.


翻译:山东省立医院风湿免疫科  张立民(624929872@qq.com


校正:孙红胜



目的:强直性脊柱炎(AS)是一种慢性炎症性疾病,病因不明,IL-17在AS发病中具有关键作用。探讨IL-17的细胞来源及诱导剂对理解AS的炎症反应至关重要。近年研究发现,黏膜相关恒定T细胞(MAIT)参与自身免疫性疾病。MAIT因其肠源性、细胞表型、表达AS相关基因(IL7R 、IL23R等)等特征,提示在AS的发病机制中具有重要作用。

方法:分离提取强直性脊柱炎(AS)患者、健康对照组(HCs)和类风湿关节炎(RA)患者血液和关节液(SF)中单个核细胞。利用流式细胞仪鉴定MAIT细胞。通过对细胞因子和颗粒酶的胞内染色鉴定细胞表型。利用沙门氏菌激活抗原特异性途径,并利用IL-7或IL-23激活抗原非特异性途径,以评价细胞功能。

结果:与HCs相比,AS患者血中MAIT细胞减少,但IL-17A + MAIT细胞比率升高。在AS关节液中MAIT细胞富集,且IL-17水平升高。AS患者MAIT细胞IL-17水平升高与IL-7的诱导有关,而与IL-23或抗原刺激无关。在该研究中,与AS相关的IL7R基因单核苷酸多态性(SNP),位点rs11742270,对IL-7R的表达无影响。

结论:该研究揭示,MAIT细胞在AS发病中的潜在作用,首次发现IL-7通过AS相关风险基因IL7R 与AS中IL-17高表达关联。

附原文OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R, makes them potential contributors to the pathogenesis of AS.METHODS: Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella, or antigen non-specific activation via priming with IL-7 or IL-23. RESULTS: MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed. CONCLUSIONS:This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.

引自Gracey E, Qaiyum Z, Almaghlouth I, et al.. IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, whichcontribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis. 2016 May 10.