Moore, CarolinaTejon, GabrielaFuentes, CamilaHidalgo, YessiaBono, Maria R.Maldonado, PaulaFernandez, RicardoWood, Kathryn J.Fierro, Juan A.Rosemblatt, MarioSauma, DanielaBushell, Andrew2023-07-172023-07-172015-02European Journal of Immunology Volume 45, Issue 2, Pages 452 - 4631 February 20150014-2980https://repositorio.unab.cl/xmlui/handle/ria/51692Indexación: ScopusCD4+CD25+Foxp3+ regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3+ T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen-specific immunosuppressive capacity in a skin allograft model in immunodeficient mice. Altogether, these data indicate that functional and stable allogeneic-specific Treg cells may be generated using TGF-β, RA, and IL-2. Thus, RA-iTreg cells may have a potential use in the development of more effective cellular therapies in clinical transplantation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.enAllogeneic regulatory T cellsHomingRetinoic acidToleranceTransplantationArtículoAttribution 4.0 International (CC BY 4.0)10.1002/eji.201444743