Research paperMesenchymal stem cells overexpressing IL-35 effectively inhibit CD4+ T cell function

- IL-35 gene modified MSCs were constructed by lentivirus transfection and can produce large amounts of IL-35 in vitro.
- IL-35-MSCs can inhibit the proliferation of CD4+ T cells and IL-17A secretion.
- IL-35-MSCs also can induce IL-10 production by CD4+ T cells, but did not affect IFN-γ.
- IL-35-MSCs can increase the proportion of CD4+Foxp3+Treg cells.

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.