Fc?R (the receptors for IgG) are important for pathogenesis in antibody-driven autoimmunity. Fc?RIIa is the most abundant and widespread human Fc-receptor.
We have shown that human Fc?RIIa expressed in appropriate cellular distributions at physiological levels in transgenic mice is sufficient to confer susceptibility to collagen-induced arthritis and spontaneous multi-system autoimmunity. We are currently investigating the molecular and cellular basis of Fc?RIIa-driven autoimmunity.
The presence of Fc?RIIa lowers the threshold of activation of innate immune cells by autoantibodies that drive the effector arm of pathogenic inflammation. We can completely inhibit the progress of this information by targeting FcgRIIa with either newly designed drugs or engineered monoclonal antibodies.
Our research shows that targeting this receptor at the right time can prevent the progress of the disease and that T cells secreting the proinflammatory cytokine IL-17 are elevated in Fc?RIIa-transgenic mice. We are now investigating if Fc?RIIa plays a role in skewing adaptive immunity.
- Structural basis for Fc gammaRIIa recognition of human IgG and formation of inflammatory signaling complexes.
Ramsland PA, Farrugia W, Bradford TM, Sardjono CT, Esparon S, Trist HM, Powell MS, Tan PS, Cendron AC, Wines BD, Scott AM, Hogarth PM
J Immunol. 2011 Aug
- Inhibition of destructive autoimmune arthritis in FcgammaRIIa transgenic mice by small chemical entities.
Pietersz GA, Mottram PL, de Velde NCV, Sardjono CT, Esparon S, Ramsland PA, Moloney G, Baell JB, McCarthy TD, Matthews BR, Powell MS, Hogarth PM
Immunol Cell Biol. 2009 Jan; 87(1):3-12
- Development of spontaneous multisystem autoimmune disease and hypersensitivity to antibody-induced inflammation in Fcgamma receptor IIa-transgenic mice.
Tan Sardjono C, Mottram PL, van de Velde NC, Powell MS, Power D, Slocombe RF, Wicks IP, Campbell IK, McKenzie SE, Brooks M, Stevenson AW, Hogarth PM
Arthritis Rheum. 2005 Oct; 52(10):3220-3229
- Recombinant soluble human Fc gamma RII: production, characterization, and inhibition of the Arthus reaction.
Ierino FL, Hulett MD, McKenzie IF, Hogarth PM
J Exp Med. 1993 Nov; 178(5):1617-1628
- Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice.
Prins JB, Todd JA, Rodrigues NR, Ghosh S, Hogarth PM, Wicker LS, Gaffney E, Podolin PL, Fischer PA, Sirotina A, Peterson LB
Science. 1993 Apr; 260(5108):695-698