Transgenic mice expressing human FcgammaRIIa have enhanced sensitivity to induced autoimmune arthritis as well as elevated Th17 cells.
The major human Fc receptor, huFcgammaRIIa, is implicated in the development of autoimmune arthritis in humans but until recently has not been studied in mouse models. We evaluated potential roles of FcgammaRIIa by using transgenic mice expressing the receptor. We examined two models of induced autoimmune arthritis pristane-induced arthritis (PIA) and collagen-induced arthritis (CIA) as well as the anti-collagen-II antibody-induced arthritis (CAIA) model. In the induced arthritis models PIA and CIA, the transgenic mice developed a more severe arthritis than the other arthritis-prone SJL or DBA1 mice. Interestingly, anti-collagen-II antibodies were elevated in PIA in the susceptible mice. In the CIA model, the highly susceptible transgenic mouse had IgG subclass levels equivalent to the unaffected and disease resistant C57BL/6 mouse strain implying that the FcgammaRIIa lowers the threshold of IgG dependent leukocyte activation. This is consistent with the greatly enhanced sensitivity of the FcgammaRIIa transgenic mice to CAIA which clearly indicates a role for the receptor at least at the inflammatory effector cell level. Other roles for huFcgammaRIIa or other gene products in the development of autoimmunity cannot be ruled out however, especially as the mice exhibited elevated Th1 or Th17 CD4 T cells in the draining lymph nodes.
Van de Velde
Nicholas C
NC
Helen Macpherson Smith Laboratory, Burnet Institute, Melbourne, VIC, Australia.
Mottram
Patricia L
PL
Powell
Maree S
MS
Lim
Bock
B
Holmdahl
Rikard
R
Hogarth
P Mark
PM
D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
C080568:Fc gamma receptor IIA; D020381:Interleukin-17; D017452:Receptors, IgG; D007371:Interferon-gamma