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The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss.
Nat. Immunol. 13, 465-473 (2012)
Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
3.914
3.914
123
300
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Sprache
englisch
Veröffentlichungsjahr
2012
HGF-Berichtsjahr
0
ISSN (print) / ISBN
1529-2908
e-ISSN
1529-2916
Zeitschrift
Nature Immunology
Quellenangaben
Band: 13,
Heft: 5,
Seiten: 465-473
Verlag
Nature Publishing Group
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
PubMed ID
22447028
DOI
10.1038/ni.2260
Erfassungsdatum
2012-12-31