Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow-226014, India.
Clin Rheumatol. 2022 Aug;41(8):2297-2308. doi: 10.1007/s10067-022-06202-2. Epub 2022 May 11.
It is now well established that Th17 lymphocytes associate with myriad immune-mediated inflammatory diseases. Over the past one and a half decades, a subset of Th17 lymphocytes viz. Th17.1 lymphocytes has been identified in pre-clinical and clinical models of inflammatory rheumatic diseases. These lymphocytes secrete IL-17A (signature cytokine of Th17 lymphocytes) as well as IFN-γ (the signature cytokine of Th1 lymphocytes). They express the chemokine markers for Th1 (CXCR3) as well as Th17 (CCR6) lymphocytes. Th17.1 lymphocytes also express the drug efflux protein p-glycoprotein, which associates with resistance to corticosteroids and other immunosuppressive drugs. This narrative review overviews the evidence regarding Th17.1 lymphocytes in different inflammatory rheumatic diseases. It is now recognized that Th17.1 lymphocytes are increased in the synovial fluid of affected joints in rheumatoid arthritis (RA) and associate with poor treatment response to abatacept. Th17.1 lymphocytes from synovial fluid of RA are less responsive to immunosuppression than those from the peripheral blood. In sarcoidosis, Th17.1 lymphocytes are concentrated in mediastinal lymph nodes and alveolar lining. Such Th17.1 lymphocytes in sarcoidosis are the predominant source of IFN-γ in the sarcoid lung. Th17.1 lymphocytes are elevated in lupus and Takayasu arteritis and associate with disease activity. Future studies should evaluate isolated Th17.1 lymphocytes from peripheral blood or sites of pathology such as synovial fluid and assess their modulation with immunosuppressive therapy in vitro. The analysis of gene expression signature of isolated Th17.1 lymphocytes might enable the identification of newer therapeutic strategies specifically targeting these cell populations in inflammatory rheumatic diseases. Key Points • Th17.1 lymphocytes are a subset of Th17 lymphocytes secreting both IFN-γ and IL-17 • Th17.1 lymphocytes drive neutrophilic inflammation, granuloma formation, and corticosteroid resistance • Th17.1 lymphocytes are elevated in rheumatoid arthritis and sarcoidosis at sites of inflammation • Increased circulating Th17.1 lymphocytes have been identified in lupus and Takayasu arteritis and associate with active disease.
现在已经证实，Th17 淋巴细胞与多种免疫介导的炎症性疾病有关。在过去的十五年中，在炎症性风湿性疾病的临床前和临床模型中已经鉴定出 Th17 淋巴细胞的一个亚群，即 Th17.1 淋巴细胞。这些淋巴细胞分泌 IL-17A（Th17 淋巴细胞的特征性细胞因子）以及 IFN-γ（Th1 淋巴细胞的特征性细胞因子）。它们表达 Th1（CXCR3）和 Th17（CCR6）淋巴细胞的趋化因子标记物。Th17.1 淋巴细胞还表达药物外排蛋白 P-糖蛋白，这与对皮质类固醇和其他免疫抑制药物的耐药性有关。本综述概述了不同炎症性风湿性疾病中 Th17.1 淋巴细胞的证据。现在已经认识到，类风湿关节炎（RA）受累关节滑液中 Th17.1 淋巴细胞增多，并与阿巴西普治疗反应不良相关。来自 RA 滑膜液的 Th17.1 淋巴细胞比来自外周血的 Th17.1 淋巴细胞对免疫抑制的反应性更低。在结节病中，Th17.1 淋巴细胞集中在纵隔淋巴结和肺泡衬里。结节病中的这种 Th17.1 淋巴细胞是结节病肺中 IFN-γ的主要来源。狼疮和 Takayasu 动脉炎中 Th17.1 淋巴细胞升高，并与疾病活动相关。未来的研究应从外周血或滑膜液等病理部位分离出 Th17.1 淋巴细胞，并评估其在体外与免疫抑制治疗的调节作用。分离的 Th17.1 淋巴细胞的基因表达特征分析可能使我们能够确定针对炎症性风湿性疾病中这些细胞群体的新的治疗策略。关键点 • Th17.1 淋巴细胞是分泌 IFN-γ和 IL-17 的 Th17 淋巴细胞的一个亚群 • Th17.1 淋巴细胞驱动中性粒细胞炎症、肉芽肿形成和皮质类固醇耐药性 • Th17.1 淋巴细胞在类风湿关节炎和结节病的炎症部位升高 • 在狼疮和 Takayasu 动脉炎中发现循环 Th17.1 淋巴细胞升高，并与活动期疾病相关。
