IFN-γ and IL-33 modulate mesenchymal stem cells function targeting Th1/Th17 axis in a murine skin transplantation model.

The immune regulatory properties of IL-33 have indicated that this cytokine has the capacity to target several immune cells under a variety of immunological responses, including overt inflammation and tolerance. Due to its versatile mechanistics, we sought to investigate the role of IL-33 on mesenchymal stem cells (MSC), a population of cells with recognizable modulatory functions. Our data indicates that IL-33 does not affect the expression of classical MSC markers such as CD29, CD44 and CD73, or the lack of CD45, CD11b and CD117. Also, we found that IL-33 greatly induces iNOS expression and stimulates the secretion of TGF-β and IL-6. Next, we decided to test IFN-γ/IL-33-treated MSC using a skin transplantation model. Our data indicate that allogeneic skin-grafted animals treated with IFN-γ/IL-33-modulated MSC reject as controls. Complementing this finding, we observed that ex vivo re-stimulated draining lymph nodes (dLN) cells from these mice secrete lower amounts of IFN-γ and a slightly higher amount of IL-17. Beside a reduction in CD4+ and CD8+ T cells number, we preliminarily found an increment in the frequencies of CD4+Foxp3+IL-17+ T cells. Altogether, our data propose that IL-33 and IFN-γ modulate MSC phenotype and function, most likely targeting Th1/Th17 axis.