Open Access Green as soon as Postprint is submitted to ZB.
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.
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1529-2908
Journal Nature Immunology
Quellenangaben Volume: 13, Issue: 5, Pages: 465-473
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)