Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints and other organs for which there is currently no effective treatment. Mesenchymal stem cells (MSCs) have therapeutic potential due to their immunomodulatory and differentiation effects. While extensive experimental studies and clinical trials have demonstrated the effects of MSCs in various diseases, MSCs have been found to cause abnormal differentiation and tumor formation. Therefore, extracellular vesicles derived from MSCs (MSC-EVs) are more effective, less toxic, and more stable than the parental cells. MSC-EVs transfer various nucleic acids, proteins, and lipids from parent cells to recipient cells, and thus participate in chronic inflammatory and immune processes. In this review, we summarize the properties and biological functions of MSCs and MSC-EVs in RA. Improvement in our understanding of the mechanisms underlying MSC and MSC-EVs in RA provides an insight into potential biomarkers and therapeutic strategies for RA.

Numerous patients with rheumatoid arthritis (RA) manifest severe syndromes, including elevated synovial fluid volumes (SF) with abundant immune cells, which can be controlled by TNF/JAK inhibitors. Here, we apply single-cell RNA sequencing (scRNA-seq) and subsequent validations in SF from RA patients. These analyses of synovial tissue show reduced density of SF-derived pathogenic cells (e.g., SPP1⁺ macrophages and CXCL13⁺CD4⁺ T cells), altered gene expression (e.g., SPP1 and STAT1), molecular pathway changes (e.g., JAK/STAT), and cell-cell communications in drug-specific manners in samples from patients pre-/post-treated with adalimumab/tofacitinib. Particularly, SPP1⁺ macrophages exhibit pronounced communication with CXCL13⁺CD4⁺ T cells, which are abolished after treatment and correlate with treatment efficacy. These pathogenic cell types alone or in combination can augment inflammation of fibroblast-like synoviocytes in vitro, while conditional Spp1 knocking-out reduces RA-related cytokine expression in collagen-induced arthritis mice models. Our study shows the functional role of SF-derived pathogenic cells in progression and drug-specific treatment outcomes in RA.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints. The central pathogenesis of RA is the proliferation of synovial fibroblasts in response to inflammatory cytokines. However, some of the targeted therapies for inflammation reactions do not display significant clinical improvement after initiation of therapy. Thus, the relationship between inflammatory responses and RA therapy is still incompletely understood. In the present study, we proposed to determine whether enhanced inflammations may lead to cell apoptosis in rheumatoid arthritis synoviocytes. Our results indicated that products of lipid peroxidations, 4‐HNE, may induce synovial intrinsic inflammations by activating NF‐κB pathways and it may lead to cell apoptosis. Pharmacological inhibition of NF‐κB activation may reduce the 4‐HNE mediated inflammation responses and subsequent cell apoptosis. Our results may help to clarify the role of inflammations on RA development and imply that blocking NF‐κB activation may be partly beneficial for human RA therapy. These findings might provide a mechanism‐based rationale for developing new strategy to RA clinical therapy.

Autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, spondyloarthritis (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), are characterized by chronic immune activation and systemic inflammation. The systemic immune-inflammation index (SII), computed as platelet count × neutrophil count/lymphocyte count, is a promising biomarker that reflects both inflammatory burden and immune dysregulation. In RA, elevation of SII is correlated with disease activity score, response to TNF-α inhibitors, and reduced serum Klotho levels. In AS and PsA, the SII is associated with disease activity scores, musculoskeletal imaging findings, and treatment response. In SLE, the SII tracks global activity and predicts lupus nephritis and pregnancy outcomes, while further reflecting underlying features, such as lymphopenia, neutrophil extracellular trap formation, and platelet activation. The SII is also useful in vasculitis-related diseases, including Behçet’s syndrome and Kawasaki disease. In comparison to traditional markers such as CRP and ESR, the SII provides broader immune insights than routine hematologic data. SII is influenced by non-autoimmune factors, including malignancy and infection, which are often excluded from autoimmune studies, although significant in clinical interpretation. This review summarizes the latest evidence on the SII across autoimmune conditions. It also aims to outline the key limitations and future directions, including longitudinal validation, integration with emerging indices (e.g., the systemic inflammatory response index), and its role in multimodal disease monitoring.

Chimeric antigen receptor T (CAR-T) cells are T cells engineered to express specific synthetic antigen receptors that can recognize antigens expressed by tumor cells, which after the binding of these antigens to the receptors are eliminated, and have been adopted to treat several kinds of malignancies. Autoimmune diseases (AIDs), a class of chronic disease conditions, can be broadly separated into autoantibody-mediated and T cell-mediated diseases. Treatments for AIDs are focused on restoring immune tolerance. However, current treatments have little effect on immune tolerance inverse; even the molecular target biologics like anti-TNFαinhibitors can only mildly restore immune balance. By using the idea of CAR-T cell treatment in tumors, CAR-T cell-derived immunotherapies, chimeric autoantibody receptor T (CAAR-T) cells, and CAR regulatory T (CAR-T) cells bring new hope of treatment choice for AIDs.