STIM1 is essential for Fcgamma receptor activation and autoimmune inflammation.

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.
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)
Chemical References	Antigen-Antibody Complex Autoantibodies Calcium Channels Immunoglobulin G Membrane Glycoproteins Receptors, IgG Stim1 protein, mouse Stromal Interaction Molecule 1 Calcium
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!