The effect of all‐trans retinoic acid (ATRA) and mesenchymal stem cells (MSCs) transplantation on increased expression of Foxp3 and IL‐10

PURPOSE: It has been known that MSCs have the capability of regenerating organs, as well as modulating immune function. Recent studies suggest that the vitamin A metabolite, ATRA is capable of promoting anti‐inflammatory Treg cell differentiation. With this, we analyzed expressional changes of CD4+CD25+Foxp3+Tregs with mice injected MSCs and/or ATRA. METHOD: MSCs (1×10 6 ) prepared from C57BL/6 mice bone marrow were adoptively transferred into syngenic mice via a tail vein. After one day, the MSCs injected mice were I.P. immunized with OVA (100 μg/mouse) and Alum (1 mg). After immunization, ATRA (10 mg/kg) was I.P. injected everyday. Two weeks after postimmunization, we obtained spleen cells and measured Treg cells related markers of CD4, CD25, Foxp3 and cytokine pofiles of IL‐10, IL‐4, IL‐12 and IFN‐r by flow cytometry analysis. RESULTS: Compared to the group that did not undergo MSCs transplantation, the group that received transplantation showed to have a high expression of Foxp3 within the spleen cells, and more so with ATRA‐treatment. Also, expressions of IL‐4 and IL‐10 were higher in the group with that received transplantation and more so in the ATRA‐treated group. CONCLUSION: MSCs and ATRA treatment might have immunomodulatory effet in immunized mice through the up‐regulation of Foxp3 and IL‐10 expression.