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

Area of Science:

• Immunology
• Cell Biology
• Gene Therapy

Background:

• Mesenchymal stem cells (MSCs) are explored for cell-based immune tolerance therapy.
• Interleukin 35 (IL-35) is a cytokine crucial for regulatory T cell (Treg) function and autoimmune disease prevention.

Purpose of the Study:

• To investigate the immunosuppressive potential of adipose tissue-derived MSCs engineered for Interleukin 35 (IL-35) overexpression.
• To evaluate the impact of IL-35-overexpressing MSCs on CD4+ T cell proliferation and cytokine production.

Main Methods:

• Isolation of adipose tissue-derived MSCs.
• Transfection of MSCs with a lentivirus vector for murine IL-35 gene overexpression.
• Quantification of IL-35 levels using ELISA.
• Co-culture experiments with CD4+ T cells and IL-35-MSCs.

Main Results:

• IL-35 overexpression was confirmed in transfected MSCs.
• IL-35-MSCs significantly inhibited CD4+ T cell proliferation and IL-17A secretion.
• IL-35-MSCs induced IL-10 production in CD4+ T cells, without affecting IFN-γ levels.

Conclusions:

• MSCs overexpressing IL-35 exhibit augmented immunosuppressive properties compared to unmodified MSCs.
• This IL-35-MSC gene therapy strategy offers a promising avenue for autoimmune disorder research and treatment.