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.

Publications

2011

• 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

2010

• Transgenic mice expressing human FcgammaRIIa have enhanced sensitivity to induced autoimmune arthritis as well as elevated Th17 cells.
  Van de Velde NC, Mottram PL, Powell MS, Lim B, Holmdahl R, Hogarth PM
  Immunol Lett. 2010 May; 130(1-2):82-88

2009

• 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

2006

• Alteration of the Fc gamma RIIa dimer interface affects receptor signaling but not ligand binding.
  Powell MS, Barnes NC, Bradford TM, Musgrave IF, Wines BD, Cambier JC, Hogarth P
  J Immunol. 2006 Jun; 176(12):7489-7494

2005

• 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

1999

• Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa.
  Maxwell KF, Powell MS, Hulett MD, Barton PA, McKenzie IF, Garrett TP, Hogarth PM
  Nat Struct Biol. 1999 May; 6(5):437-442

1995

• Recombinant soluble Fc gamma RII inhibits immune complex precipitation.
  Gavin AL, Wines BD, Powell MS, Hogarth PM
  Clin Exp Immunol. 1995 Dec; 102(3):620-625

1993

• 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