The Role of Allogeneic Stem Cell Therapy in Treatment of Refractory Rheumatoid Arthritis by Immunomodulating the Treg and Th17 Balance
Introduction. Rheumatoid Arthritis (RA) is a chronic progressive autoimmune disease which primarily affects the distal articular joints, and especially the hands.1 The interaction of heritable risk factors like HLA-DR04, and environmental risk factors such as smoking, promote a loss of immune tolerance for self-antigens which leads to immune activation of osteoclasts that mediate synovial inflammation and joint destruction.2 TNF-alpha and IL-6 inhibitors are new drugs that can inhibit pro-inflammatory cytokines. Recent research centers have focused on the potential of mesenchymal stem cells to restore the balance between pro-inflammatory Th17 cells and anti- inflammatory Treg cells. Methods. Bone marrow mesenchymal stem cells (BM-MSCs) were isolated from eleven patients with RA and eight healthy controls (HC). Researchers used a collagen II induced arthritis (CIA) model in DBA/1 mice and treated them with HC and RA BM-MSCs.3 They also compared levels of the anti- inflammatory A20 protein and pro-inflammatory IL-6 cytokine in healthy controls and RA patients. Similarly, A20 and IL-6 were also compared in control mice (not CIA) and CIA mice before and after treatment with HC and RA human BM-MSCs. Results. HC serum expressed higher levels of A20 mRNA and lower levels of IL-6 mRNA than RA serum, p<0.001 and p<0.01 respectively. CIA mice treated with HC UC-MSCs expressed higher levels of A-20 than untreated CIA mice (p<0.05) and lower levels of IL-6 (p<0.001).3 Conclusions. MC show promise in treating severe RA unresponsive to biological disease modifying anti-rheumatic drugs (bDMARDs). A20 helps inhibit the action of TNF-alpha activation of the NF-kB pathway which drives production of IL-6 and furthers inflammation. In RA, the balance between Th17 and Treg cells is broken, which inhibits A20 and upregulates IL-6.3 More research exploring the loss of anti-inflammatory A20 in RA and how treatment with MSC restores A20 levels by alleviating the Th17 and Treg imbalance may provide additional advancements in treatment.
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