The Leukocyte Integrin Antagonist Del-1 Inhibits IL-17-mediated Inflammatory Bone Loss

Overview

Journal Nat Immunol

Date 2012 Mar 27

PMID 22447028

Citations 235

Authors

Mehmet A Eskan

Ravi Jotwani

Toshiharu Abe

Jindrich Chmelar

Jong-Hyung Lim

Shuang Liang

Paul A Ciero

Jennifer L Krauss

Fenge Li

Martina Rauner

Lorenz C Hofbauer

Eun Young Choi

Kyoung-Jin Chung

Ahmed Hashim

Michael A Curtis

Triantafyllos Chavakis

George Hajishengallis

Affiliations

Soon will be listed here.

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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