The role of FcγRs in inflammation during infection and autoimmunity

Fc receptors (FcRs) have recently emerged as a family of receptors that are important for shaping immune responses. In this thesis, we specifically focused on Fc gamma receptors (FcγRs), which recognize both immunoglobulin G (IgG) and pentraxins such as C-reactive protein (CRP). The aim of the research project underlying this thesis was to investigate the role of FcγRs in inflammation during infection and chronic inflammatory disorders. We investigated this by studying the immune responses from both healthy donors and patients. We identified that FcγR activation by both IgG antibodies and CRP shapes inflammatory responses. We showed that FcγRs cooperate with different kinds of PRRs to control cytokine production by human myeloid immune cells. This results in enhanced anti-bacterial responses in the context of bacterial infections, and negative feedback by suppression of type I IFNs in the case of viral infections. In addition, we identified that dysregulation of these pathways can contribute to the pathogenesis of autoimmune diseases. We showed that FcγR-induced cytokine production is dysregulated in lupus nephritis patients, resulting in enhanced inflammation. Taken together, we further established that FcγRs play an important role in inflammation in both host defense responses as well as in autoimmune diseases. Further elucidation of the downstream pathways could provide new therapeutic opportunities to enhance pathogen-specific immune responses and/or to attenuate inflammation in the case of several immune disorders.