“…The most efficient antigen presenting cells (APCs) in activating T cells and initiating immune tolerance are the DCs. Based on different surface markers, DCs are generally divided into three subsets: (i) DCs involved in ischemia-reperfusion injury (IRI) and expressing C1d, CD8α, CD11c, CD40, CD45, CD54 (ICAM), CD80, CD86, MHC-II, and TNFα, but are negative for CD4 and CD205 ( 101 ); when activated by antigens released during ischemia-reperfusion, these DCs can trigger both cellular and antibody-mediated rejection, resulting in harmful antibodies secretion by activated B cells and killing of donor cells by cytotoxic T cells ( 102 ); (ii) rejection-related DCs, promoting acute and chronic rejection via different interactions with T cells and are characterized by the expression of CD11c, MHC-II, CD1c and FcϵRI ( 103 ); (iii) tolerogenic DCs, suppressing the rejection process by dampening the T cell effector functions and promoting T regulatory cells (Tregs) activity; these DCs express significantly lower levels of MHC, T cell co-stimulatory molecules, such as CD40, and CD80/86, and inhibitory ligands, such as programmed death ligand-1 (PD-L1) and death-inducing ligands, reflecting their non-phagocytic profile ( 104 , 105 ). In response to specific signals such as DAMPs, host DCs can acquire a rejection-related phenotype, which can further evolve towards a tolerogenic phenotype upon treatment with rapamycin, IL-10, vitamin D, or low-dose granulocyte-macrophage colony-stimulation factor (GM-CSF).…”