Metalloproteinases and their natural inhibitors in inflammation and immunity

R Khokha, A Murthy, A Weiss - Nature Reviews Immunology, 2013 - nature.com
R Khokha, A Murthy, A Weiss
Nature Reviews Immunology, 2013nature.com
Over the past 50 years, steady growth in the field of metalloproteinase biology has shown
that the degradation of extracellular matrix components represents only a fraction of the
functions performed by these enzymes and has highlighted their fundamental roles in
immunity. Metalloproteinases regulate aspects of immune cell development, effector
function, migration and ligand–receptor interactions. They carry out ectodomain shedding of
cytokines and their cognate receptors. Together with their endogenous inhibitors TIMPs …
Abstract
Over the past 50 years, steady growth in the field of metalloproteinase biology has shown that the degradation of extracellular matrix components represents only a fraction of the functions performed by these enzymes and has highlighted their fundamental roles in immunity. Metalloproteinases regulate aspects of immune cell development, effector function, migration and ligand–receptor interactions. They carry out ectodomain shedding of cytokines and their cognate receptors. Together with their endogenous inhibitors TIMPs (tissue inhibitor of metalloproteinases), these enzymes regulate signalling downstream of the tumour necrosis factor receptor and the interleukin-6 receptor, as well as that downstream of the epidermal growth factor receptor and Notch, which are all pertinent for inflammatory responses. This Review discusses the metalloproteinase family as a crucial component in immune cell development and function.
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