Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Front Immunol. 2019 Aug 21;10:1989. doi: 10.3389/fimmu.2019.01989. eCollection 2019.
In rheumatoid arthritis (RA), various hematopoietic and non-hematopoietic cells present in the synovial tissue secrete numerous inflammatory mediators including pro-inflammatory cytokines critical for the induction of chronic joint inflammation and bone destruction. Fibroblast-like synoviocytes (FLSs) in the non-hematopoietic cell compartment are key inflammatory cells activated in inflamed joints and driving the disease; yet how synovial tissue inflammation is modulated by autoimmune T cells is not fully understood. In this review, mainly based on recent findings with a mouse model of spontaneous autoimmune arthritis, we discuss the mechanism of Th17-mediated synovial tissue inflammation; that is, what environmental stimuli and arthritogenic self-antigens trigger arthritis, how arthritogenic T cells initiate joint inflammation by stimulating FLSs, and how the cellular sources of GM-CSF from lymphoid and tissue stromal cells in the synovium contribute to the development of arthritis. We also highlight possible plasticity of Th17 cells toward pathogenic GM-CSF producers, and the functional instability of regulatory T cells under inflammatory conditions in RA joints.
在类风湿关节炎（RA）中，滑膜组织中的各种造血和非造血细胞分泌大量炎症介质，包括促炎细胞因子，这些细胞因子对于诱导慢性关节炎症和骨质破坏至关重要。非造血细胞群中的成纤维样滑膜细胞（FLS）是在炎症关节中被激活的关键炎症细胞，驱动着疾病的发展；然而，自身免疫 T 细胞如何调节滑膜组织炎症尚不完全清楚。在这篇综述中，主要基于自发性自身免疫性关节炎小鼠模型的最新发现，我们讨论了 Th17 介导的滑膜组织炎症的机制；即，什么环境刺激和致关节炎自身抗原引发关节炎，致关节炎 T 细胞如何通过刺激 FLS 引发关节炎症，以及滑膜中淋巴样和组织基质细胞来源的 GM-CSF 的细胞来源如何促进关节炎的发展。我们还强调了 Th17 细胞向致病性 GM-CSF 产生细胞的可能可塑性，以及 RA 关节中炎症条件下调节性 T 细胞的功能不稳定性。
