Indoleamine-2,3-dioxygenase (IDO) Mediates the Suppression of T Cells by IFN-γ Primed Mesenchymal Stromal Cells in the Treatment of Psoriasis-Like Inflammation.

Abstract

Background: Psoriasis is a chronic and incurable skin inflammation driven by an abnormal immune response. Our study aims to investigate the potential of interferon-γ (IFN-γ) primed mesenchymal stem cells (IMSCs) in targeting T cells to attenuate psoriasis-like inflammation, and to elucidate the underlying molecular mechanism involved.

Methods: Mesenchymal stem cells (MSCs) were isolated from the umbilical cord and identified based on their surface markers. Psoriasis models were established and then treated with IMSCs. Flow cytometry analysis was used to examine cell surface markers and T cell percentages. Indoleamine-2,3-dioxygenase (IDO) was knocked down by small interfering RNA (siRNA) and examined with western blot assay. The proliferative capacity of T cells was assessed using water-soluble tetrazolium salt-1(WST-1). Additionally, an immunohistochemical assay was used to determine epidermal thickness. The psoriasis area and severity index (PASI) scores were also assessed.

Results: We observed significant therapeutic efficacy of IMSCs against psoriasis-like inflammation in mice. Treatment with IMSCs resulted in a notable reduction in T cell infiltration within psoriatic lesions. Furthermore, we demonstrated that the therapeutic efficacy was mediated by the upregulation of IDO through IFN-γ stimulation. In vitro, IDO inhibited T cell proliferation, and in vivo, the therapeutic efficacy was eliminated when MSCs were transfected with IDO siRNA.

Conclusion: IMSCs can treat psoriasis by suppressing T cell infiltration and the suppression is mediated by IDO.