Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC–T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Faslpr mice.
The level of VEGF in aqueous humor was significantly higher in the failure group after the Ahmed glaucoma implantation compared with the success group. Our results imply that VEGF may play a role in determining surgical success after Ahmed valve implantation in patients with NVG.
Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.
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