Fig. 3.

Cellular processes involved in the pathogenesis of autoimmunity. Tissue damage during autoimmunity contributes to, and can result from, a chronic forward-feeding pathophysiological network involving the innate immune system. The perturbed clearance of dead cells or improper regulation of apoptosis can be an underlying factor in autoimmune disease. The intracellular/nuclear debris released from dead cells may form immune complexes with autoantibodies. Free intracellular debris, including DAMPS (e.g., nucleic acids) is recognized by TLR-family receptors, whereas the Fc portion of autoantibodies in immune-complexes are recognized by Fc receptors (FcRs) on myeloid cells. This in turn induces the expression of pro-inflammatory cytokines (e.g., IFNs, IL-6, TNFα), which contribute to other pathophysiological processes, including enhanced tissue remodeling/damage, autoreactive adaptive immune response, and inflammatory response of other innate immune cells in the affected tissues.