STIM1 is essential for Fcgamma receptor activation and autoimmune inflammation

Attila Braun; J Engelbert Gessner; David Varga-Szabo; Shahzad N Syed; Stephanie Konrad; David Stegner; Timo Vögtle; Reinhold E Schmidt; Bernhard Nieswandt

doi:10.1182/blood-2008-05-158477

STIM1 is essential for Fcgamma receptor activation and autoimmune inflammation

Blood. 2009 Jan 29;113(5):1097-104. doi: 10.1182/blood-2008-05-158477. Epub 2008 Oct 21.

Authors

Attila Braun¹, J Engelbert Gessner, David Varga-Szabo, Shahzad N Syed, Stephanie Konrad, David Stegner, Timo Vögtle, Reinhold E Schmidt, Bernhard Nieswandt

Affiliation

¹ Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.

PMID: 18941110
DOI: 10.1182/blood-2008-05-158477

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen-Antibody Complex / genetics
Antigen-Antibody Complex / immunology*
Autoantibodies / genetics
Autoantibodies / immunology
Autoimmune Diseases / genetics
Autoimmune Diseases / immunology*
Autoimmune Diseases / pathology
Calcium / immunology
Calcium Channels
Female
Humans
Immunoglobulin G / genetics
Immunoglobulin G / immunology
Inflammation / genetics
Inflammation / immunology
Inflammation / pathology
Macrophages / immunology*
Macrophages / pathology
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / immunology*
Mice
Mice, Knockout
Phagocytosis / genetics
Phagocytosis / immunology*
Receptors, IgG / genetics
Receptors, IgG / immunology*
Signal Transduction / genetics
Signal Transduction / immunology
Stromal Interaction Molecule 1

Substances

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