Environmental triggers and endogenous alarmins linking innate immunity to the pathogenesis of type 1 diabetes

Similar as other autoimmune diseases, a characteristic feature for type 1 diabetes (T1D) is the selective targeting of a specific type of cells, the insulin secreting β cells of the islets of Langerhans in the pancreas, by a certain population of autoreactive immune cells. Given the importance of innate immunity in triggering and/or tuning autoimmunity by modulating adaptive immune responses to self-antigens, its role in T1D pathogenesis has long been proposed. However, due to the challenge for identifying which cells, receptors and mediators associated with innate immunity are critical in T1D associated autoimmune settings, much research and attention have been focused on T cell mediated adaptive immune responses for the past few decades, while the implication of innate immunity in disease related etiology has almost been completely neglected. Recently, compelling evidence derived from the studies carried out in both animal models and T1D patients had consistently highlighted the importance of innate immunity in T1D etiology. In this chapter, we will review and discuss the progress on environmental triggers and endogenous alarmins linking innate immunity to the pathogenesis of type 1 diabetes. We will use HMGB1, an evolutionarily conserved endogenous danger signal, as an example to discuss the possible implications of innate immunity in autoimmune initiation and progression during T1D development, as well as islet allograft rejection in diabeticpatients after islet transplantation, which may provide an insight into the development of novel therapeutic strategies for type 1 diabetes.