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

被引：338

作者：

Eskan, Mehmet A. ^{[1
,8
]}

Jotwani, Ravi ^{[1
]}

Abe, Toshiharu ^{[1
]}

Chmelar, Jindrich ^{[2
,3
]}

Lim, Jong-Hyung ^{[2
,3
]}

Liang, Shuang ^{[1
]}

Ciero, Paul A. ^{[1
]}

Krauss, Jennifer L. ^{[1
]}

Li, Fenge ^{[1
]}

Rauner, Martina ^{[4
]}

Hofbauer, Lorenz C. ^{[4
]}

Choi, Eun Young ^{[2
,3
,5
,6
]}

Chung, Kyoung-Jin ^{[2
,3
]}

Hashim, Ahmed ^{[7
]}

Curtis, Michael A. ^{[7
]}

Chavakis, Triantafyllos ^{[2
,3
,6
]}

Hajishengallis, George ^{[1
,8
]}

机构：

[1] Univ Louisville, Sch Dent, Ctr Oral Hlth & Syst Dis, Louisville, KY 40292 USA

[2] Tech Univ Dresden, Dept Med, Div Vasc Inflammat Diabet & Kidney, D-01062 Dresden, Germany

[3] Tech Univ Dresden, Inst Physiol, D-01062 Dresden, Germany

[4] Tech Univ Dresden, Dept Med, Div Endocrinol Diabet & Bone Dis, D-01062 Dresden, Germany

[5] Univ Ulsan, Grad Sch, Dept Med, Seoul, South Korea

[6] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA

[7] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Immunol & Infect Dis, Blizard Inst, London, England

[8] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 05期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

PERIODONTAL-DISEASE; IN-VITRO; T-CELLS; NEUTROPHILS; IL-17; INTERLEUKIN-17; RECRUITMENT; MIGRATION; CHEMOKINE; CYTOKINE;

D O I：

10.1038/ni.2260

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：465 / U64

页数：10

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