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Publication : ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity.

First Author  McMahon M Year  2016
Journal  PLoS Biol Volume  14
Issue  11 Pages  e1002580
PubMed ID  27855162 Mgi Jnum  J:239748
Mgi Id  MGI:5829600 Doi  10.1371/journal.pbio.1002580
Citation  McMahon M, et al. (2016) ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity. PLoS Biol 14(11):e1002580
abstractText  The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5-/- mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality.
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