| Literature DB >> 32646852 |
Elisabeth Salzer1,2,3,4, Samaneh Zoghi1,2,3,5,6, Máté G Kiss3,7, Frieda Kage8,9, Christina Rashkova1,3,10, Stephanie Stahnke9, Matthias Haimel1,2,3, René Platzer11, Michael Caldera3, Rico Chandra Ardy1,2,3, Birgit Hoeger1,2,3, Jana Block1,2,3, David Medgyesi1, Celine Sin3, Sepideh Shahkarami5,12,13, Renate Kain14, Vahid Ziaee15,16, Peter Hammerl17, Christoph Bock1,3, Jörg Menche3, Loïc Dupré1,18, Johannes B Huppa11, Michael Sixt19, Alexis Lomakin1,2,3, Klemens Rottner8,9, Christoph J Binder3,7, Theresia E B Stradal9, Nima Rezaei5,6,20, Kaan Boztug21,1,3,4,10.
Abstract
The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1-/- mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity.Entities:
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Year: 2020 PMID： 32646852 PMCID： PMC7116756 DOI： 10.1126/sciimmunol.abc3979
Source DB: PubMed Journal: Sci Immunol ISSN： 2470-9468