ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23

• Published in: Nature Immunology Vol. 7; no. 12; pp. 1293 - 1298
• Main Authors: Blobel, Carl P, Weskamp, Gisela, Ford, Jill W, Sturgill, Jamie, Martin, Steve, Docherty, Andrew J P, Swendeman, Steven, Broadway, Neil, Hartmann, Dieter, Saftig, Paul, Umland, Shelby, Sehara-Fujisawa, Atsuko, Black, Roy A, Ludwig, Andreas, Becherer, J David, Conrad, Daniel H
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2006
• Subjects: ADAM Proteins - immunology; ADAM Proteins - metabolism; ADAM10 Protein; Amyloid Precursor Protein Secretases - immunology; Amyloid Precursor Protein Secretases - metabolism; Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts - immunology; Fibroblasts - metabolism; Flow Cytometry; Humans; Immunoblotting; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Mice, Knockout; Receptors, IgE - immunology; Receptors, IgE - metabolism; Transfection
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1399

CD23, the low-affinity immunoglobulin E receptor, is an important modulator of the allergic response and of diseases such as rheumatoid arthritis. The proteolytic release of CD23 from cells is considered a key event in the allergic response. Here we used loss-of-function and gain-of-function experiments with cells lacking or overexpressing candidate CD23-releasing enzymes (ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19 and ADAM33), ADAM-knockout mice and a selective inhibitor to identify ADAM10 as the main CD23-releasing enzyme in vivo. Our findings provide a likely target for the treatment of allergic reactions and set the stage for further studies of the involvement of ADAM10 in CD23-dependent pathologies.