The diverging roles of dendritic cells in kidney allotransplantation.

Dendritic cells (DCs) are a family of antigen presenting cells that play a paramount role in bridging innate and adaptive immunity. In murine models several subtypes of DCs have been identified, including classical DCs, monocyte-derived DCs, and plasmacytoid DCs. Quiescent, immature DCs and some subtypes of plasmacytoid cells favor the expression of regulatory T cells, but in an inflammatory milieu DCs become mature and after intercepting the antigen migrate to lymphatic system where they present the antigen to naïve T cells. Transplant rejection largely depends on the phenotype and maturation of DCs. The ischemia-reperfusion injury causes the release of endogenous molecules that are recognized as danger signals by the pattern recognition receptor of the innate immunity with subsequent activation of inflammatory cells and mediators. In this environment DCs become mature and migrate to lymphonodes where they present the alloantigen to T cells and direct their differentiation towards Th1 and Th17 effector cells. On the other hand, manipulation of DCs may favor T cell differentiation towards tolerant Th2 and T regulators (Treg). Experimental studies in murine models showed the possibility of inducing an operational tolerance by injecting immature tolerogenic DCs. Recently, such a possibility has been also confirmed in primates. Although manipulation of DCs may represent an important step ahead in kidney transplantation, a number of technical and ethical issues should be solved before its clinical application.