Schinnerling K, Aguillón J C, Catalán D, Soto L
Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Clin Exp Immunol. 2017 Jul;189(1):12-20. doi: 10.1111/cei.12966. Epub 2017 Apr 20.
Therapeutic blockage of cytokine signalling in autoimmune diseases has improved our understanding of the role of these cytokines in triggering, shaping and perpetuating autoimmune responses. In rheumatoid arthritis (RA), immunopathology is driven by a predominance of arthritogenic T helper cells secreting interferon-γ [T helper type 1 (Th1)] and interleukin (IL)-17 (Th17) over regulatory T cells (T ). The pleiotropic cytokine IL-6 is crucial to the differentiation of Th17 cells and the balance between pathogenic Th17 and protective T . Targeting the IL-6 receptor (IL-6R) by humanized antibodies improves signs and symptoms of RA, and has provided new insights into the mechanisms of inflammation and immune regulation. Here we review current evidence on the role of IL-6 in the pathogenesis of RA and the molecular consequences of IL-6R blockage in disease, with special focus on the Th17/T balance and plasticity.
在自身免疫性疾病中对细胞因子信号传导进行治疗性阻断，增进了我们对这些细胞因子在引发、形成和维持自身免疫反应中所起作用的理解。在类风湿性关节炎（RA）中，免疫病理学是由分泌干扰素-γ的致关节炎辅助性T细胞[1型辅助性T细胞（Th1）]和白细胞介素（IL）-17（Th17）相对于调节性T细胞（Treg）占优势所驱动的。多效性细胞因子IL-6对于Th17细胞的分化以及致病性Th17细胞与保护性Treg细胞之间的平衡至关重要。通过人源化抗体靶向IL-6受体（IL-6R）可改善RA的体征和症状，并为炎症和免疫调节机制提供了新的见解。在此，我们综述了关于IL-6在RA发病机制中的作用以及IL-6R阻断在疾病中的分子效应的现有证据，特别关注Th17/Treg平衡和可塑性。
