Human Herpes simplex 1 virus infection of endometrial decidual tissue-derived MSC alters HLA-G expression and immunosuppressive functions

Objectives: Mesenchymal stromal/stem cells have immunosuppressive functions. Our previous results demonstrated that one of the players of this immunomodulation can be ascribed to the Human Leukocyte Antigen-G. HLA-G, a non classical HLA class I antigen, is involved in immune tolerance during pregnancy, organ transplantation, autoimmune and inflammatory diseases. In this study we wanted to verify whether human endometrial decidual tissue derived (EDT)-MSC could express HLA-G. Additionally we assessed the permissivity to Human Herpesvirus infections, using HSV-1 as a model, and the possible effect on EDT-MSC immunosuppressive functions towards peripheral blood mononuclear cell (PBMC) proliferation. Methods: We analyzed immune-inhibitory functions and HLA-G expression in human EDT-MSC before and after HSV-1 infection. Results: We observed that EDT-MSC express HLA-G molecules, that partly are responsible for the immune-inhibitory functions of EDT-MSC towards PBMC proliferation. EDT-MSC are permissive for a productive infection by HSV-1, that decreases HLA-G expression and affects EDT-MSC immune-inhibitory functions. Conclusions: We demonstrate that EDT-MSC are susceptible to HSV-1 infection, that reduces HLA-G expression and their immune-inhibitory function. These data could have a clinical implication in the use of EDT-MSC as an immunosuppressant, in particular in steroid-refractory GvHD after allogeneic hematopoietic stem cell transplantation and in autoimmune diseases.