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Critical contribution of T cell‐derived MMPs to influenza virus pathology
Author(s) -
Baaten Bas J. G.,
Lin Melissa M.,
Hughes Chris C. W.,
Bradley Linda M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1072.2
Subject(s) - matrix metalloproteinase , biology , pathogenesis , immunology , mmp9 , basement membrane , virus , immunity , inflammation , immune system , virology , microbiology and biotechnology , gene , biochemistry , downregulation and upregulation
Influenza viruses cause significant annual illness and death with recurrent seasonal epidemics and sporadic devastating pandemics. The efficiency of highly pathogenic influenza viruses has been attributed to potent and aberrant inflammatory responses, which can result in severe immunopathological damage and death in humans. T cells can contribute to pulmonary damage by direct lysis of infected cells and the production of pro‐inflammatory cytokines. Migration of T cells and their effector responses in situ are crucial steps towards immunity, but could also contribute to the high morbidity and mortality associated with pathogenic strains. We hypothesized that the ability of T cells to efficiently cross the lung endothelial barrier and move through the basement membrane, which is essential for their function, is regulated by matrix metalloproteases (MMPs). MMPs have the proteolytic capability to mediate cleavage of the collagen network that makes up the basement membrane. We demonstrate that T cells express MMP2 and MMP9 activity, which is crucial during influenza virus‐induced pathogenesis. Furthermore, we discuss the factors that affect the induction of MMPs in T cells. The discovery of the roles of MMPs in T cell function during influenza virus pathogenesis could elucidate the balance between immunity and pathology and may therefore have considerable therapeutic relevance.