STAT3: a potential therapeutic target in dendritic cells for the induction of transplant tolerance

Dendritic cells (DCs) control the segue from innate to adaptive immunity. Moreover, depending upon their milieu, DCs can either induce or inhibit immune responses. Whether DCs are immune stimulatory or tolerogenic apparently rests with whether or not the DCs express activated signal transducer and activator of transcription-3 (STAT3), the transcription factor induced by IL-6-like cytokines and IL-10. DCs expressing activated STAT3 produce less IL-12, which results in less effector T cell development. Moreover, DCs expressing activated STAT3 also express the tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase. The kynurenine products of tryptophan catabolism induce T cell apoptosis; this area is of major interest to researchers working on tolerogenic DCs. In various disease models ranging from tumours to autoimmune diseases, administration of STAT3-activating cytokines resulted in attenuation of immune responses. Other corroborating evidence was obtained using conditional STAT3-deficient mice, or mice defective in cytokine signalling. Thus, persistently activating STAT3 in DCs may be a feasible strategy for controlling allograft rejection.