Aryl hydrocarbon receptor in mesenchymal stem cells is required for the therapeutic efficacy of graft vs host disease in mice

초록

The Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is induced by the toxicity of environmental pollutants. It is implicated in the regulation of the immune system also a balance between inflammatory and suppressive/regulatory T cell activity. Mesenchymal stem cells (MSCs) have immunomodulatory activities, including suppression of T- and B-cell activation. MSC-mediated immunosuppression occurs via nitric oxide (NO) in mice. Here, we isolated MSCs from Ahr-/- bone marrow in mice and found less immunosuppressive function and produce less inducible nitric oxide synthase (iNOS) compared to the wild type (WT)-MSCs. Since MSCs have been used for the treatment of graft-vs-host disease (GvHD), we injected the WT and AhR-deficient MSCs into the GvHD mice. The AhR-deficient MSCs showed less therapeutic efficacy compared to the WT MSCs. It suggests that the deficiency of the AhR gene in MSC showed less immunosuppressive function. Thus, our result indicated that AhR is involved in the production of Nitric oxide (NO) via regulating iNOS expression which is required for the therapeutic efficacy of MSCs.