A significant decrease of BAFF, APRIL, and BAFF receptors following mesenchymal stem cell transplantation in patients with refractory rheumatoid arthritis

Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, the formation of pannus and the destruction of cartilage. The global incidence of RA is about 1%, and it is more common in women. The basic feature of RA is the body’s immune system disorders, in which autoreactive CD4+T cells, pathogenic B cells, M1 macrophages, inflammatory cytokines, chemokines and autoantibodies abnormally increase in the body of RA patients B cell depletion therapy has well proved the important role of B cells in the pathogenesis of RA, and the treatment of RA with B cells as a target has also been paid more and more attention. Although the inflammatory indicators in RA patients receiving B-cell depletion therapy have been significantly improved, the risk of infection and cancer has also increased, which suggests that we need to deplete pathogenic B cells instead of all B cells. However, at present we cannot distinguish between pathogenic B cells and protective B cells in RA patients. In this review, we explore fresh perspectives upon the roles of B cells in the occurrence, development and treatment of RA.

Section: Targeted B Cell Checkpointsmentioning

confidence: 99%

B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects

Gao

Kang

et al. 2021

“…In mouse models with collagen-induced arthritis (CIA), the administration of human AT-derived MSCs (AT-MSCs) inhibited the differentiation of activated CD4+ T cells into T helper (Th) 17 effector cells producing interleukin (IL)-17, but induced the generation of T regulatory cells (Tregs) that secrete IL-10 and negatively regulate the immune response (30). Similar beneficial effects have been reported in RA animal models using various MSC treatments (28,31,32). The effects of MSCs on Th17/Treg cell balance have been attributed to various soluble molecules, including indoleamine 2,3-dioxygenase (IDO), IL-10, prostaglandin E2 (PGE2), and nitric oxide (NO), and to the transfer of organelles (32,33).…”

Section: Immunomodulatory Effect Of Mscs In Ramentioning

confidence: 73%

“…In the past decade, MSC transplantation (MSCT) has been found to be effective in the treatment of RA by reducing joint inflammation, bone erosion, and destruction and alleviating the formation of pannus via immune regulation, anti-inflammation, and differentiation (28,29). MSCs mainly interact with both innate and adaptive immune cells to modulate immune responses in RA.…”

Section: Immunomodulatory Effect Of Mscs In Ramentioning

confidence: 99%

Immunomodulatory Effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Rheumatoid Arthritis

Liu

et al. 2020

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.

“…Interestingly, MSCs were reported to express BAFF both in mRNA and protein (127), indicating that MSCs might have the ability to induce Bregs via secreting BAFF. In clinical studies, MSCs are shown to decrease the plasma levels of BAFF in patients with cGVHD or refractory rheumatoid arthritis (RA), accompanied with regulating the activity of B cells and alteration in B cell subpopulation (128,129). However, more experiments still need to confirm the BAFF-mediated effects on MSCs inducing Bregs, and reveal the underling mechanisms.…”

Section: B Cell-activating Factor (Baff)mentioning

confidence: 99%

The Immunomodulatory Effects of Mesenchymal Stem Cells on Regulatory B Cells

Liu

2020

The therapeutic potential of mesenchymal stem cells (MSCs) has been investigated in many preclinical and clinical studies. This potential is dominantly based on the immunosuppressive properties of MSCs. Although the therapeutic profiles of MSC transplantation are still not fully characterized, accumulating evidence has revealed that B cells change after MSC infusion, in particular inducing regulatory B cells (Bregs). The immunosuppressive effects of Bregs have been demonstrated, and these cells are being evaluated as new targets for the treatment of inflammatory diseases. MSCs are capable of educating B cells and inducing regulatory B cell production via cell-to-cell contact, soluble factors, and extracellular vesicles (EVs). These cells thus have the potential to complement each other's immunomodulatory functions, and a combined approach may enable synergistic effects for the treatment of immunological diseases. However, compared with investigations regarding other immune cells, investigations into how MSCs specifically regulate Bregs have been superficial and insufficient. In this review, we discuss the current findings related to the immunomodulatory effects of MSCs on regulatory B cells and provide optimal strategies for applications in immune-related disease treatments.