The emergence of ADAM10 as a regulator of lymphocyte development and autoimmunity

Proteolytic processing of transmembrane receptors and ligands can have a dramatic impact on cell signaling processes and subsequent cellular responses, including activation and differentiation. A member of the disintegrin and metalloproteinase family, ADAM10, has emerged as a prominent regulator of numerous receptors and ligands, including Notch and CD23. Here, we review studies resulting from the recent generation of ADAM10 conditional knockout mice which revealed a critical role for ADAM10 in Notch-dependent lymphocyte development. Additionally, we discuss results of numerous in vitro and ex vivo studies indicating that ADAM10 regulates the production of multiple secreted factors that contribute to autoimmune reactions. (C) 2010 Elsevier Ltd. All rights reserved.