Quantcast

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

Research paper by Mehmet A MA Eskan, Ravi R Jotwani, Toshiharu T Abe, Jindrich J Chmelar, Jong-Hyung JH Lim, Shuang S Liang, Paul A PA Ciero, Jennifer L JL Krauss, Fenge F Li, Martina M Rauner, Lorenz C LC Hofbauer, Eun Young EY Choi, Kyoung-Jin KJ Chung, Ahmed A Hashim, Michael A MA Curtis, et al.

Indexed on: 27 Mar '12Published on: 27 Mar '12Published in: Nature Immunology



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.

More like this: