Fc receptor activation controls cytokine expression by human antigen-presenting cells

Myeloid antigen presenting cells (APC), are important directors of the human immune system. Crucial for the induction of both innate and adaptive immunity by myeloid APCs is the production of various cytokines. The ultimate cytokine profile that is produced, and therefore the ultimate immune response that is induced, critically depends on collaboration between multiple families of receptors. In this thesis, we investigated the role of Fc receptors, mainly Fc gamma receptor IIa (FcγRIIa) and Fc alpha receptor I (FcαRI), in controlling cytokine production by myeloid APCs. We show that Fc receptors cooperate with Toll-like receptors (TLR) to control cytokine production of APCs. FcR-TLR cross-talk leads to enhanced anti-bacterial responses, however with clear distinctions between cell-types. In addition, we show that the same mechanism can be erroneously activated in autoimmune diseases and could contribute to the pathogenesis of rheumatoid arthritis and inflammatory bowel disease. Taken together, antibodies via Fc receptors control cytokine production in human APCs in health and disease. Identification of this mechanism uncovers new therapeutic strategies for autoimmune disorders.