Abstract
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota.
Highlights
Introduction to RARheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1% of the population worldwide, caused by abnormal immune activation and immune tolerance and characterized by synovial inflammation, cartilage damage, and bone destruction [1]
We have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and immunomodulatory cell (IC), and further discussed the strategies for treating RA by targeting/regulating the gut microbiota
Evans-Marin et al showed that CD4+ T cells in the lamina propria were activated before the onset of arthritis in mice with collagen-induced arthritis (CIA), following the significant upregulation of IL-17A, tumor necrosis factor- (TNF-) α, and granulocyte-macrophage colony-stimulating factor (GMCSF), and the severity of arthritis was significantly reduced if T helperMediators of Inflammation17 (Th17) cells were lacking [18]
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1% of the population worldwide, caused by abnormal immune activation and immune tolerance and characterized by synovial inflammation, cartilage damage, and bone destruction [1]. Previous studies have suggested that immune abnormalities, such as immunomodulatory cell (IC) activation or inhibition, that take place at a local and, subsequently, at a systemic level are present in patients who are at risk of developing RA [2]. A memory B cell subset that expresses the immunoglobulin A (IgA) receptor, termed Fc receptor-like 4 (FcRL4), is a component of the local autoimmune response that can contribute to the joint destruction in RA patients via receptor activation of nuclear factor-κB ligand (RANKL) expression [14]. During the development of RA, the intestinal mucosal immune response is excessively exaggerated, antigen-presenting cells (APCs) are abnormally activated, and immune tolerance is disturbed. The decreased mucosal immunity to citrullinated proteins/peptides and the recruitment of new B cells are crucial features of antirheumatic therapy responses in early RA patients [19]. We summarize the roles of the gut microbiota in the pathogenesis and treatment of RA, focusing on the interactions between the gut microbiota and intestinal ICs
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