RGD Reference Report - Destructive arthritis in the absence of both FcgammaRI and FcgammaRIII. - Rat Genome Database

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Destructive arthritis in the absence of both FcgammaRI and FcgammaRIII.

Authors: Boross, P  Van Lent, PL  Martin-Ramirez, J  Van der Kaa, J  Mulder, MH  Claassens, JW  Van den Berg, WB  Arandhara, VL  Verbeek, JS 
Citation: Boross P, etal., J Immunol. 2008 Apr 1;180(7):5083-91.
RGD ID: 5508446
Pubmed: PMID:18354234   (View Abstract at PubMed)

Fc receptors for IgG (FcgammaR) have been implicated in the development of arthritis. However, the precise contribution of the individual FcgammaR to joint pathology is unclear. In this study, the role of the different FcgammaR was assessed both in an active and in a passive mouse model of arthritis by analyzing disease development in double and triple knockout (KO) offspring from crosses of FcgammaRI KO, FcgammaRIII KO, FcgammaRI/III double KO, or FcR gamma-chain KO with the FcgammaRII KO on C57BL6 background, which is susceptible for collagen-induced arthritis (CIA). In the active CIA model, onset was significantly delayed in the absence of FcgammaRIII, whereas incidence and maximum severity were significantly decreased in FcgammaRI/II/III triple KO but not in FcgammaRII/III double KO and FcgammaRI/II double KO mice as compared with FcgammaRII KO animals. Remarkably, fully destructive CIA developed in FcgammaRI/II/III triple KO mice. In contrast, FcR gamma/FcgammaRII double KO mice were resistant to CIA. These findings were confirmed with the passive KRN serum-induced arthritis model. These results indicate that all activating FcgammaR play a role in the development of arthritis, mainly in the downstream effector phase. FcgammaRIII is critically required for early arthritis onset, and FcgammaRI can substantially contribute to arthritis pathology. Importantly, FcgammaRI and FcgammaRIII were together dispensable for the development of destructive arthritis but the FcR gamma-chain was not, suggesting a role for another FcR gamma-chain associated receptor, most likely FcgammaRIV. In addition, FcgammaRII plays a negative regulatory role in both the central and effector phase of arthritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanExperimental Arthritis onsetISOFcgr3 (Mus musculus) RGD 
Fcgr2aRatExperimental Arthritis onsetISOFcgr3 (Mus musculus) RGD 
Fcgr3MouseExperimental Arthritis onsetIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)

Additional Information