Fc receptors and their interaction with complement in autoimmunity.
Genetic studies in mice indicate a crucial role for Fc receptors (FcR) in antibody-mediated autoimmune diseases. Like other immune regulatory receptor pairs, the FcR system is constituted by activating and inhibitory receptors that bind the same ligand, the Fc portion of Ig. Analyses of animal models have shown that the inhibitory Fc receptor, FcgammaRIIB can suppress antibody-mediated autoimmunity, whereas activating-type FcR, such as FcgammaRIII promote disease development. This review summarizes recent advances of FcR, as obtained from gene deletion studies in mice, and highlights the importance of factors that interact with FcR in autoimmunity. There is emerging evidence for an indispensable role of the complement component C5a in the regulation of FcR and the sensing of FcR-dependent effector cell responses. On the other hand, FcR might be alternatives to serum complement in the generation of C5a at sites of inflammation. Thus, FcR and complement interact with each other at the level of C5a by linking regulatory events with effector cell activities in autoimmunity. This connecting pathway is now proposed to be a promising new therapeutic target for the treatment of inflammation and autoimmune disease in both mice and humans.
Schmidt
Reinhold E
RE
Abteilung für Klinische Immunologie, Medizinische Hochschule Hannover, Labor für Molekulare Immunologie, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Gessner
J Engelbert
JE
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D003167:Complement Activation / Q000235:genetics / Q000276:immunology*; D015936:Complement C5a / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051379:Mice; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; D015936:Complement C5a