Targeting Innate Immunity for Type 1 Diabetes Prevention.

PURPOSE OF REVIEW: Despite immense research efforts, type 1 diabetes (T1D) remains an autoimmune disease without a known trigger or approved intervention. Over the last three decades, studies have primarily focused on delineating the role of the adaptive immune system in the mechanism of T1D. The discovery of Toll-like receptors in the 1990s has advanced the knowledge on the role of the innate immune system in host defense as well as mechanisms that regulate adaptive immunity including the function of autoreactive T cells.

RECENT FINDINGS: Recent investigations suggest that inflammation plays a key role in promoting a large number of autoimmune disorders including T1D. Data from the LEW1.WR1 rat model of virus-induced disease and the RIP-B7.1 mouse model of diabetes suggest that innate immune signaling plays a key role in triggering disease progression. There is also evidence that innate immunity may be involved in the course of T1D in humans; however, a small number of clinical trials have shown that interfering with the function of the innate immune system following disease onset exerts only a modest effect on β-cell function. The data implying that innate immune pathways are linked with mechanisms of islet autoimmunity hold great promise for the identification of novel disease pathways that may be harnessed for clinical intervention. Nevertheless, more work needs to be done to better understand mechanisms by which innate immunity triggers β-cell destruction and assess the therapeutic value in blocking innate immunity for diabetes prevention.