Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 2, Pages 764-774Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.2.764
Keywords
-
Categories
Ask authors/readers for more resources
Type I diabetes mellitus (TID) in humans is an organ-specific autoimmune disease in which pancreatic islet 6 cells are ruptured by autoreactive T cells. NOD mice, the most commonly used animal model of TID, show early infiltration of leukocytes in the islets (insulitis), resulting in islet destruction and diabetes later. NOD mice produce various islet 13 cell-specific autoantibodies, although it remains a subject of debate regarding whether these autoantibodies contribute to the development of TID. Fc gamma Rs 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 gamma Rs in NOD mice, we generated several Fc gamma R-less NOD lines, namely FcR common gamma-chain (FcR gamma)-deficient (NOD.gamma(-/-)), Fc gamma RIII-deficient (NOD.III-/-), Fc gamma RIII-deficient (NOD.IIB-/-), and both FcR gamma and Fc gamma RIIB-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 gamma Rs on dendritic cells enhance autoantigen presentation leading to the activation of autoreactive T cells, and Fc gamma RIII on NK cells trigger Ab-dependent effector functions and inflammation. These findings highlight the critical roles of activating Fc gamma Rs in the development of TID, and indicate that Fc gamma Rs are novel targets for therapies for TID.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available