Synovial Tissue Inflammation Mediated by Autoimmune T Cells

• Main Authors: Yusuke Takeuchi, Keiji Hirota, Shimon Sakaguchi
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-08-01
• Series: Frontiers in Immunology
• Subjects: autoimmune arthritis; Th17; treg cells; rheumatoid arthritis; synovial inflammation; proinflammatory cytokine
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2019.01989/full

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.