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Nat Immunol. 2012 Mar 25;13(5):465-73. doi: 10.1038/ni.2260.

The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss.

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1
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.

Abstract

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.

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PMID:
22447028
PMCID:
PMC3330141
DOI:
10.1038/ni.2260
[Indexed for MEDLINE]
Free PMC Article

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