Clipping, shedding and RIPping keep immunity on cue.
Exposure to infectious agents elicits defense mechanisms that necessitate a timely immune response. The immediate delivery of essential cues for immune activation is provided, in part, by proteolytic processing. A large repertoire of molecules orchestrates the activation, migration, and effector function of immune cells. The diversity of this repertoire matches well with the broad array of substrates that can be cleaved by proteinases, and many of these substrates are proving to be essential for proper immune-cell function. Here, we discuss how two specific classes of metal-dependent proteinases, the matrix metalloproteinases and the disintegrin metalloproteinases, have consequences well beyond classical cell-matrix and cell-cell interactions and motility, and we review their roles in immune-cell maturation, clonal expansion, and cytotoxic functions.
Murphy
Gillian
G
Department of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Cambridge, UK. gm290@cam.ac.uk
Murthy
Aditya
A
Khokha
Rama
R
D000818:Animals; D000917:Antibody Formation; D002465:Cell Movement; D019483:Disintegrins / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000276:immunology / Q000378:metabolism*
D019483:Disintegrins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases