ERN1 and Autoimmunity: IRE1α plays a major role in ER stress-mediated autoimmunity development possibly through five different mechanisms (Figure 3): including misfolded proteins identification by autoreactive immune cells, peptides released from apoptotic cells acting as neoantigens/autoantigens, disturbed immune-tolerance mechanisms increases ERAD-associated proteins that give the survival advantage to autoreactive cells (193), and reduced antigen presentation.