Understanding the Role of the Unfolded Protein Response Sensor IRE1 in the Biology of Antigen Presenting Cells

The unfolded protein response (UPR) is an adaptive response that maintains the fidelity of the cellular proteome in conditions that subvert the folding capacity of the cell, such as those noticed in infection and inflammatory contexts. In immunity, the UPR sensor IRE1 (Inositol-requiring enzyme 1-alpha) has emerged as a critical regulator of the homeostasis of antigen presenting cells (APCs). In the past few years, it has become clear that IRE1 plays canonical and non-canonical roles in APCs, many of which intersect with key features of these cells, including the initiation of inflammation, antibody production, and antigen presentation. The aims of the present review are to provide recent insights on the mechanisms by which IRE1 regulates the diversity of APC functions and to highlight its relevance in the coordination of innate and adaptive immunity.