Fc receptors and the common gamma-chain in experimental autoimmune encephalomyelitis.
Fcgamma receptors (FcgammaRs), composed of a ligand-binding alpha-chain (FcRalpha) sometimes associated with the homodimeric, cell-signaling common gamma-chain (FcRgamma), comprise an important family of effector molecules linking humoral and cell-mediated adaptive immunity and regulating innate immunity. In peripheral autoimmune diseases, FcgammaRs contribute to inflammation and tissue damage through inappropriate activation of macrophages and neutrophils, release of cytokines and oxidants, and destruction of autoantibody-opsonized cells. In the central nervous system (CNS), the role of FcgammaRs in autoimmune disease such as multiple sclerosis (MS) remains largely unexplored despite extensive documentation of CNS-specific antibodies in cerebrospinal fluid and plaques. Several studies have now examined the role of FcgammaRs in experimental autoimmune encephalomyelitis (EAE), the animal model for MS, using mice genetically deficient in one or more FcgammaRs or in FcRgamma. These studies indicate that none of the FcgammaR alpha-chains are critical for EAE development and progression. In contrast, it is unequivocal that FcRgamma contributes to EAE, and surprisingly it seems that this effect is independent of FcgammaRs. Recent studies now indicate that FcRgamma expression in gammadelta T cells, most likely as a component of the TCR/CD3 signaling complex, is a critical requirement for EAE development. These studies support previous evidence implicating a pathogenic role for gammadelta T cells in EAE.
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Alexander J
AJ
Szalai
Scott R
SR
Barnum
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009103:Multiple Sclerosis / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG