All-trans retinoic acid favors the development and function of regulatory T cells from liver transplant patients

Graft-versus-host disease (GVHD) is an intractable complication in transplant patients. Regulatory T cells (Tregs) have the ability to prevent GVHD and consist of two subsets: natural Tregs (nTregs) and induced Tregs (iTregs). In comparison to nTregs, iTregs originate in the periphery under certain conditions and show improved proliferative and suppressive abilities in an inflammatory milieu. All-trans retinoic acid (atRA) favors Treg expansion and FoxP3 expression in human Tregs. However, whether atRA can affect the function of iTregs from transplant patients remains inconclusive. Therefore, we sorted naïve T cells from liver transplant patients and cultured them in vitro. Further analyses were performed to assess the suppressive function of iTregs in vitro and in vivo. atRA favored expansion and forkhead box P3 expression in iTregs from transplant patients. In comparison to iTregs from healthy donors, iTregs from transplant patients showed decent suppressive abilities in vitro and in vivo. Our findings suggest that atRA can potentially improve the development and function of iTregs from transplant patients. Furthermore, our results provide novel insights into Treg therapy in GVHD clinical trials.