Rheumatoid arthritis (RA), the most common of the autoimmune arthropathies, is characterized by inflammation of the synovial lining of the joints (synovitis) and involvement of systemic tissues and organs such as the lungs, ultimately causing progressive joint destruction and severe disability. Over the last three decades, RA treatment strategies have advanced dramatically, which enabled physicians to ease RA symptoms with better control of cartilage and bone damage. This new era in therapeutics has been led by the emergence of a number of biological disease-modifying antirheumatic drugs (bDMARDs), since the role of several key proinflammatory cytokines including TNF-a and IL-6, and cell-associated targets such as CD20 and co-stimulation molecules CD80/86 in arthritis have been clarified. Despite these successes, however, no cure as yet exists; many of the key fundamentals underlying the immunopathology of RA still remain unknown. Thus, further pathogenetic discoveries are yet required to drive more specific immunological therapy, leading to the recovery of immune homeostasis to achieve cure of the disease.
Autoimmunity has been implicated in the pathogenesis of RA since the discovery of rheumatoid factors (anti-IgG antibodies) in sera from patients. Accumulating evidence for the etiology of RA has suggested RA as a multifactorial disease involving multiple mechanisms: genetic influence; disordered innate immunity including immune complex-mediated complement activation; adaptive immune responses against self-antigens comprising post-translationally modified proteins; dysregulated cytokine networks; osteoclast and chondrocyte activation; and imprinting of resident stromal cells that support disease progression. Most notably, the pathological hallmark of RA is synovitis with proliferating fibroblasts and infiltrating immunocompetent cells, in which a wide range of cells are found including CD4+ T cells, CD8+ T cells, B cells, and myeloid cells consisting of monocytes/macrophages in large numbers. In addition to our increased knowledge about a variety of helper T cell subsets, recent evidence has robustly expanded our understanding of the role of macrophages in disease pathology. Macrophages play a pivotal role in the induction and resolution of inflammatory diseases. Active RA involves M1 polarized pro-inflammatory macrophages which stimulate continual activation and result in tissue remodeling via stromal cells. Therapeutic intervention induces re-polarization of M1 to the anti-inflammatory M2 phenotypes. Furthermore, the interplay between CD4+ T cells and monocytes/macrophages has also been suggested. Given the interdependent complex of macrophage and T cell immunity, further investigation in this regard is warranted, especially in terms of external modulations, which will provide novel insight into revolutionary advances in therapeutics for RA.
In this Research Topic we aim to expand the current understanding of the pathogenesis of RA by compiling high-value articles, thereby promoting further research into this important area of study. We therefore welcome the submission of manuscripts (Original Research, Review, and Mini-Review articles) which are relevant but are not limited to the following subjects:
- Phenotypic analysis of immunocompetent cells in the development of RA
- Characterization of T cells in both active RA and remission
- Characterization of monocytes/macrophages in active RA and remission
- Clonal changes and its molecular analysis on T cell recruitment during the development of RA
- The interaction between T helper cell polarization and monocytes/macrophages
- Modulation of T cell function by monocytes/macrophages
- Monocytes/macrophages activation by T cells
- Plasticity of macrophages in RA
- M1/M2 macrophage polarization in RA
- Disease activities and transition of phenotypes of T cells and monocytes/macrophages in RA
- Disease activities and transition of functions of T cells and monocytes/macrophages in RA
- Early precision or prediction of RA development by analysis of T cells and monocytes/macrophages
- Therapeutic intervention and its effects on T cells in RA
- Therapeutic intervention and its effects on monocytes/macrophages in RA
- Pharmacological modification of M1/M2 macrophage transformation
Rheumatoid arthritis (RA), the most common of the autoimmune arthropathies, is characterized by inflammation of the synovial lining of the joints (synovitis) and involvement of systemic tissues and organs such as the lungs, ultimately causing progressive joint destruction and severe disability. Over the last three decades, RA treatment strategies have advanced dramatically, which enabled physicians to ease RA symptoms with better control of cartilage and bone damage. This new era in therapeutics has been led by the emergence of a number of biological disease-modifying antirheumatic drugs (bDMARDs), since the role of several key proinflammatory cytokines including TNF-a and IL-6, and cell-associated targets such as CD20 and co-stimulation molecules CD80/86 in arthritis have been clarified. Despite these successes, however, no cure as yet exists; many of the key fundamentals underlying the immunopathology of RA still remain unknown. Thus, further pathogenetic discoveries are yet required to drive more specific immunological therapy, leading to the recovery of immune homeostasis to achieve cure of the disease.
Autoimmunity has been implicated in the pathogenesis of RA since the discovery of rheumatoid factors (anti-IgG antibodies) in sera from patients. Accumulating evidence for the etiology of RA has suggested RA as a multifactorial disease involving multiple mechanisms: genetic influence; disordered innate immunity including immune complex-mediated complement activation; adaptive immune responses against self-antigens comprising post-translationally modified proteins; dysregulated cytokine networks; osteoclast and chondrocyte activation; and imprinting of resident stromal cells that support disease progression. Most notably, the pathological hallmark of RA is synovitis with proliferating fibroblasts and infiltrating immunocompetent cells, in which a wide range of cells are found including CD4+ T cells, CD8+ T cells, B cells, and myeloid cells consisting of monocytes/macrophages in large numbers. In addition to our increased knowledge about a variety of helper T cell subsets, recent evidence has robustly expanded our understanding of the role of macrophages in disease pathology. Macrophages play a pivotal role in the induction and resolution of inflammatory diseases. Active RA involves M1 polarized pro-inflammatory macrophages which stimulate continual activation and result in tissue remodeling via stromal cells. Therapeutic intervention induces re-polarization of M1 to the anti-inflammatory M2 phenotypes. Furthermore, the interplay between CD4+ T cells and monocytes/macrophages has also been suggested. Given the interdependent complex of macrophage and T cell immunity, further investigation in this regard is warranted, especially in terms of external modulations, which will provide novel insight into revolutionary advances in therapeutics for RA.
In this Research Topic we aim to expand the current understanding of the pathogenesis of RA by compiling high-value articles, thereby promoting further research into this important area of study. We therefore welcome the submission of manuscripts (Original Research, Review, and Mini-Review articles) which are relevant but are not limited to the following subjects:
- Phenotypic analysis of immunocompetent cells in the development of RA
- Characterization of T cells in both active RA and remission
- Characterization of monocytes/macrophages in active RA and remission
- Clonal changes and its molecular analysis on T cell recruitment during the development of RA
- The interaction between T helper cell polarization and monocytes/macrophages
- Modulation of T cell function by monocytes/macrophages
- Monocytes/macrophages activation by T cells
- Plasticity of macrophages in RA
- M1/M2 macrophage polarization in RA
- Disease activities and transition of phenotypes of T cells and monocytes/macrophages in RA
- Disease activities and transition of functions of T cells and monocytes/macrophages in RA
- Early precision or prediction of RA development by analysis of T cells and monocytes/macrophages
- Therapeutic intervention and its effects on T cells in RA
- Therapeutic intervention and its effects on monocytes/macrophages in RA
- Pharmacological modification of M1/M2 macrophage transformation
