PRDM1 regulates cytokine production in CD4+ T cells and prolongs islet and skin allograft survival by regulating Th1/Th2 differentiation.

The objective of this study was to examine the effect of PRDM1 inhibition or overexpression on CD4 + T cells, and islet and skin transplantation in mice. Bioinformatics analysis revealed PRDM1 showed a significant downregulation in the Allograft group in CD4 + T cells. Mice CD4 + T cells were cultured, purified and enriched, and then transfected with shRNA lentiviral vector PRDM1-RNAi-GFP and overexpression lentiviral vector LV-PRDM1-puro. Murine islet transplantation and skin transplantation model were established, and the mice were injected with CD4 + T cells transfected with lentivirus. Levels of cytokines were measured, and the survival times of the grafts were measured and compared. T cell subsets were analyzed by flow cytometry. The expressions of IL-4 and IL-10 were up-regulated after overexpression of PRDM1, and the expression of IFN-γ was up-regulated in CD4 + T cells after inhibition of PRDM1 (P < 0.05). Overexpression of PRDM1 resulted in longer islet and skin graft survival and better graft function, while inhibition of PRDM1 shortened islet and skin graft survival. Microscopic examination showed evidence of mild rejection of islet and skin grafts in the LV-PRDM1-puro, but severe rejection in the PRDM1-RNAi group. Taken together, the results indicate that overexpression of PRDM1 can prolong graft survival and induce the formation of transplant immune tolerance via secretion of Th2 cytokines by CD4 + T cells. Inhibition of PRDM1 can promote transplant rejection and shorten graft survival via secretion of Th1 cytokines.