title: Cutting edge: Role of osteopontin and integrin αv in T cell-mediated anti-inflammatory responses in endotoxemia.
abstract: The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4(+) T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710; and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710; and Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710 mari.shinohara@duke.edu.
authors.forename: Mari L
authors.initials: ML
authors.lastname: Shinohara
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D053495:Osteopontin / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D039081:Integrin alpha5beta1; D008070:Lipopolysaccharides; D053495:Osteopontin