RGD Reference Report - Activating Fc gamma receptors participate in the development of autoimmune diabetes in NOD mice. - Rat Genome Database

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Activating Fc gamma receptors participate in the development of autoimmune diabetes in NOD mice.

Authors: Inoue, Y  Kaifu, T  Sugahara-Tobinai, A  Nakamura, A  Miyazaki, J  Takai, T 
Citation: Inoue Y, etal., J Immunol. 2007 Jul 15;179(2):764-74.
RGD ID: 5508453
Pubmed: PMID:17617565   (View Abstract at PubMed)

Type 1 diabetes mellitus (T1D) in humans is an organ-specific autoimmune disease in which pancreatic islet beta cells are ruptured by autoreactive T cells. NOD mice, the most commonly used animal model of T1D, show early infiltration of leukocytes in the islets (insulitis), resulting in islet destruction and diabetes later. NOD mice produce various islet beta cell-specific autoantibodies, although it remains a subject of debate regarding whether these autoantibodies contribute to the development of T1D. Fc gammaRs are multipotent molecules that play important roles in Ab-mediated regulatory as well as effector functions in autoimmune diseases. To investigate the possible role of Fc gammaRs in NOD mice, we generated several Fc gammaR-less NOD lines, namely FcR common gamma-chain (Fc Rgamma)-deficient (NOD.gamma(-/-)), Fc gammaRIII-deficient (NOD.III(-/-)), Fc gammaRIIB-deficient (NOD.IIB(-/-)), and both Fc Rgamma and Fc gammaRIIB-deficient NOD (NOD.null) mice. In this study, we show significant protection from diabetes in NOD.gamma(-/-), NOD.III(-/-), and NOD.null, but not in NOD.IIB(-/-) mice even with grossly comparable production of autoantibodies among them. Insulitis in NOD.gamma(-/-) mice was also alleviated. Adoptive transfer of bone marrow-derived dendritic cells or NK cells from NOD mice rendered NOD.gamma(-/-) animals more susceptible to diabetes, suggesting a possible scenario in which activating Fc gammaRs on dendritic cells enhance autoantigen presentation leading to the activation of autoreactive T cells, and Fc gammaRIII on NK cells trigger Ab-dependent effector functions and inflammation. These findings highlight the critical roles of activating Fc gammaRs in the development of T1D, and indicate that Fc gammaRs are novel targets for therapies for T1D.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumantype 1 diabetes mellitus  ISOFcgr3 (Mus musculus) RGD 
Fcgr2aRattype 1 diabetes mellitus  ISOFcgr3 (Mus musculus) RGD 
Fcgr3Mousetype 1 diabetes mellitus  IMP  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