Paulissen Sandra M J, van Hamburg Jan Piet, Dankers Wendy, Lubberts Erik
Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Cytokine. 2015 Jul;74(1):43-53. doi: 10.1016/j.cyto.2015.02.002. Epub 2015 Mar 28.
The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted.
产生白细胞介素-17A的辅助性T细胞17（Th17）群体在类风湿性关节炎（RA）发病机制中起主要作用，并作为治疗靶点引起了广泛关注。表达白细胞介素-17A的Th细胞的特征在于趋化因子受体CCR6和转录因子RORC的表达。在RA中，在外周血、滑液和炎症滑膜组织中鉴定出CCR6+ Th细胞。CCR6+ Th细胞可能会促使早期炎症发展为持续性关节炎。CCR6+ Th细胞群体是异质性的，可以区分出几个亚群，包括Th17、Th22、Th17.1（也称为非经典Th1细胞）以及未分类或中间群体。有趣的是，这些群体中的一些产生低水平的白细胞介素-17A，但仍然具有很强的致病性。此外，CCR6+ Th细胞表型不稳定，CCR6+ Th细胞与调节性T（Treg）细胞之间以及CCR6+ Th细胞亚群内部存在可塑性。在这篇综述中，讨论了不同CCR6+ Th细胞群体的特征、它们的可塑性以及它们对类风湿性关节炎的潜在影响。此外，还强调了目前针对CCR6+ Th细胞的方法以及在治疗RA患者和其他CCR6+ Th细胞介导的自身免疫性疾病中寻找特定CCR6+ Th细胞靶点的未来研究方向。
