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Eskan, M.A.* ; Jotwani, R.* ; Abe, T.* ; Chmelar, J.* ; Lim, J.H.* ; Liang, S.* ; Ciero, P.A.* ; Krauss, J.L.* ; Li, F.* ; Rauner, M.* ; Hofbauer, L.C.* ; Choi, E.Y.* ; Chung, K.-J.* ; Hashim, A.* ; Curtis, M.A.* ; Chavakis, T.* ; Hajishengallis, G.*

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

Nat. Immunol. 13, 465-473 (2012)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Quellenangaben Volume: 13, Issue: 5, Pages: 465-473 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)