Abstract |
Fcgamma receptors (FcgammaRs) on mononuclear phagocytes trigger autoantibody and immune complex-induced diseases through coupling the self-reactive immunoglobulin G ( IgG) response to innate effector pathways, such as phagocytosis, and the recruitment of inflammatory cells. FcRgamma-based activation is critical in the pathogenesis of these diseases, although the contribution of FcgammaR-mediated calcium signaling in autoimmune injury is unclear. Here we show that macrophages lacking the endoplasmic reticulum-resident calcium sensor, STIM1, cannot activate FcgammaR-induced Ca(2+) entry and phagocytosis. As a direct consequence, STIM1 deficiency results in resistance to experimental immune thrombocytopenia and anaphylaxis, autoimmune hemolytic anemia, and acute pneumonitis. These results establish STIM1 as a novel and essential component of FcgammaR activation and also indicate that inhibition of STIM1-dependent signaling might become a new strategy to prevent or treat IgG-dependent immunologic diseases.
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Authors | Attila Braun, J Engelbert Gessner, David Varga-Szabo, Shahzad N Syed, Stephanie Konrad, David Stegner, Timo Vögtle, Reinhold E Schmidt, Bernhard Nieswandt |
Journal | Blood
(Blood)
Vol. 113
Issue 5
Pg. 1097-104
(Jan 29 2009)
ISSN: 1528-0020 [Electronic] United States |
PMID | 18941110
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigen-Antibody Complex
- Autoantibodies
- Calcium Channels
- Immunoglobulin G
- Membrane Glycoproteins
- Receptors, IgG
- Stim1 protein, mouse
- Stromal Interaction Molecule 1
- Calcium
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Topics |
- Animals
- Antigen-Antibody Complex
(genetics, immunology)
- Autoantibodies
(genetics, immunology)
- Autoimmune Diseases
(genetics, immunology, pathology)
- Calcium
(immunology)
- Calcium Channels
- Female
- Humans
- Immunoglobulin G
(genetics, immunology)
- Inflammation
(genetics, immunology, pathology)
- Macrophages
(immunology, pathology)
- Male
- Membrane Glycoproteins
(genetics, immunology)
- Mice
- Mice, Knockout
- Phagocytosis
(genetics, immunology)
- Receptors, IgG
(genetics, immunology)
- Signal Transduction
(genetics, immunology)
- Stromal Interaction Molecule 1
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