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

Cell Immunol. 2017 Feb:312:61-66. doi: 10.1016/j.cellimm.2016.12.001. Epub 2016 Dec 8.

Abstract

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.

Keywords: CD4(+) T cells; Interleukin-35; Lentivirus; Mesenchymal stem cells.

MeSH terms

  • Adipose Tissue / pathology*
  • Animals
  • Autoimmune Diseases / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Humans
  • Immune Tolerance
  • Immunosuppression Therapy
  • Immunotherapy / methods*
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Interleukin-17
  • Interleukins
  • interleukin-35, mouse
  • Interleukin-10