Emerging role of innate immunity in organ transplantation part II: potential of damage-associated molecular patterns to generate immunostimulatory dendritic cells.

Part 2 of the review focuses on the potential of oxidative injury-induced damage-associated molecular patterns (DAMPs) to generate immunostimulatory dendritic cells (DCs) translating innate to adaptive immunity. Four different classes of DAMPs are defined, and their potential role in mediating pathways contributing to maturation of immunostimulatory DCs is explored and discussed. Accordingly, injury-induced molecules are divided into (1) class I DAMPs that, when recognized by pattern recognition receptors of DCs, trigger their activation; (2) class II DAMPs that are recognized by special activating receptors on innate lymphocytes that, after activation, contribute to maturation of DCs; (3) class III DAMPs that are recognized by pattern recognition receptors involved in the activation of inflammasomes, that is, molecular platforms that trigger the activation of proinflammatory cytokines promoting maturation of DCs; and (4) class IV DAMPs in terms of neoantigens that are recognized by preexisting natural immunoglobulin M antibodies, which-via complement activation-are able to aggravate the oxidative tissue injury and, thereby, may indirectly promote maturation of DCs. These new insights into mechanisms of oxidative injury-mediated generation of immunostimulatory DCs are finally discussed by addressing possible novel therapeutic strategies with the aim to prevent the capacity of oxidative injury to induce DAMPs in the donor organ. The ultimate goal of those strategies will be to induce transplant tolerance by avoiding oxidative injury in the donor and the recipient and thereby inhibiting activation of immunostimulatory DCs but promoting activation of tolerogenic DCs.