Antigen-Presenting Cells and their Fcγ and Toll-Like Receptors: Leading Suspects in Autoimmunity

Antigen-presenting cells (APCs) play an important role in the development of autoimmune diseases. These cells recognize pathogen associated molecular patterns but also endogenously produced ligands through toll-like receptors (TLRs). Aberrant activation of these receptors and the following intracellular signaling pathways can induce the deleterious production of pro-inflammatory cytokines. In genetically predisposed individuals this might lead to a breach in tolerance and eventually autoimmunity. IgG and IgG immune complexes (ICs), which are abundantly present in autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc) are recognized by APCs via Fc gamma receptors (FcγRs) and can also modulate their activation state. Upon their uptake specific antigens present in ICs are capable of stimulating APCs via their intracellular TLRs, increasing their capability to induce (autoreactive) T and B cell responses. This underscores their likely role in the generation and maintenance of autoimmunity. By focusing on three autoimmune diseases, SLE, RA and SSc, we will illustrate the importance of TLRs and FcγRs in the pathogenesis of autoimmune diseases.