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Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune tolerance therapy. Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases. In this study, we isolated adipose tissue-derived MSCs, a good vehicle for cell therapy, which were transfected with a lentivirus vector for the overexpression of the therapeutic murine IL-35 gene. IL-35 levels in transfected MSCs (IL-35-MSCs) were quantified by ELISA. Co-culture of CD4 + T cells and IL-35-MSCs resulted in the inhibition of CD4 + T cell proliferation and IL-17A secretion. In addition, IL-35-MSCs induced IL-10 production by CD4 + T cells, but did not affect IFN-γ. These findings suggested that MSCs over-expressing IL-35 had higher immunosuppressive capacity compared with non-transfected MSCs, and may provide a useful approach for basic research on gene therapy for autoimmune disorders. [ABSTRACT FROM AUTHOR]

Inducing donor-specific immunological tolerance, which avoids the complications of long-term immunosuppression, is an important goal in organ transplantation. Interleukin-35 (IL-35), a cytokine identified in 2007, is mainly secreted by regulatory T cells (Tregs) and is essential for Tregs to exert their maximal immunoregulatory activity in vitro and in vivo. A growing number of studies show that IL-35 plays an important role in autoimmune diseases and infectious diseases. Recent research has shown that IL-35 could effectively alleviate allograft rejection and has the potential to be a novel therapeutic strategy for graft rejection. With increasing study of immunoregulation, cell-based therapy has become a novel approach to attenuate rejection after transplantation. Mesenchymal stem cells (MSCs), which exhibit important properties of multilineage differentiation, tissue repair, and immunoregulation, have recently emerged as attractive candidates for cell-based therapeutics, especially in transplantation. Accumulating evidence demonstrates that the therapeutic abilities of MSCs can be amplified by gene modification. Therefore, researchers have constructed IL-35 gene-modified MSCs and explored their functions and mechanisms in some disease models. In this review, we discuss the potential tolerance-inducing effects of MSCs in transplantation and briefly introduce the immunoregulatory functions of the IL-35 gene-modified MSCs. [ABSTRACT FROM AUTHOR]