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

September 2012

Background: Periodontal disease is an infection and inflammation of the tissues surrounding and holding the teeth in place. The infection is associated with a film of bacterial plaque that builds up on the teeth and gums to cause swelling, pain, and bleeding of the tissue and even tooth loss at more advanced stages. This disease can be modeled in mice and, similar to humans, mice naturally develop periodontal disease with old age.

Advance: Periodontitis can become a chronic problem with old age. This research effort focused on the glycoprotein Del-1 (produced in blood vessel endothelium and found in gum tissue), which helps the oral tissue self-regulate local inflammation. Del-1 gene expression levels were significantly lower in older versus younger mice, and Del-1 gene knockout mice developed spontaneous gum disease. Administration of recombinant Del-1 into the gum tissue of old mice suppressed naturally occurring disease and subsequent resistance to a P. gingivalis challenge. Del-1 appears to act through two mechanisms: 1) inhibition of a protein, LFA-1, important to immune blood cell movement and inflammation, and 2) inhibition of signaling molecule IL-17, which is important in immune blood cell recruitment. Knockout of both Del-1 and IL-17 genes produced mice free of periodontal disease and demonstrated the cross-regulation of these two molecules to control inflammation.

Public Impact Statement/Significance: These research findings are paradigm-shifting by redefining inflammatory disease from one of microbial activation of inflammatory mechanisms leading to periodontal disease to one of microbial disruption of homeostatic mechanisms that control inflammatory processes.

Publication Citation and Link to Publication: Eskan MA, Jotwani R, Abe T, Chmelar J, Lim JH, Liang S, Ciero PA, Krauss JL, Li F, Rauner M, Hofbauer LC, Choi EY, Chung KJ, Hashim A, Curtis MA, Chavakis T, Hajishengallis G (2012). The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol, 13(5):465-473.

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This page last updated: February 26, 2014