The role of ERAP1 in autoinflammation and autoimmunity

Autoimmune and autoinflammatory diseases affect millions worldwide. These classes of disease involve abnormal immune activation of both the innate and adaptive immune systems. While both classes of disease represent a spectrum of aberrant immune activation, excessive activation of the innate immune system has been considered causal for the inflammation and tissue damage found in autoinflammatory diseases, while excessive activation of the adaptive immune system has been thought to primarily contribute to end-organ symptoms noted in autoimmune diseases. Interestingly, the endoplasmic reticulum aminopeptidase 1 (ERAP1) protein, well known for its aminopeptidase function as a molecular ruler, trimming peptides prior to their loading onto MHC-I molecules for antigen presentation in the ER, has also been shown to be genetically associated with both autoinflammatory and autoimmune diseases. Indeed, this multifaceted protein has been found to have many functions that affect both the innate and adaptive immune responses. In this review, we summarize these findings, with an attempt to identify the possible ERAP1 dependent mechanisms responsible for the pathogenesis of multiple, ERAP1 associated diseases.