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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 PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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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 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
PubMed ID 22447028
Erfassungsdatum 2012-12-31