Research ArticlePERIODONTITIS

Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I Disease Causes Local IL-17–Driven Inflammatory Bone Loss

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Science Translational Medicine  26 Mar 2014:
Vol. 6, Issue 229, pp. 229ra40
DOI: 10.1126/scitranslmed.3007696

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Lessening Bone Loss and Bacterial Burden

Nothing dazzles like a beautiful smile, but it’s hard to flash a red carpet–worthy grin when you have leukocyte adhesion deficiency type I (LAD-I). These patients suffer inflammatory degeneration of the bone that cradles the pearly whites (periodontium) as well as other oral pathologies. The periodontal bone loss was thought to result from a lack of neutrophil surveillance of LAD-associated frequent periodontal infections. Now, Moutsopoulos et al. show that cytokine IL-17 secreted by immune T lymphocytes drives periodontal bone loss, thus pinpointing a therapeutic target for LAD-I.

Neutrophils are white blood cells that form the first line of defense against microbial infections. These cells carry on their surfaces the LFA-1 β2 integrin (CD11a/CD18), a leukocyte adhesion molecule that is essential for neutrophil movement from the blood to peripheral tissues (extravasation) in response to infection. LAD-I is caused by mutations in the CD18 subunit of β2 integrins and is associated with frequent oral microbial infections and severe periodontal bone loss. The authors showed that defective neutrophil recruitment to the periodontal space in LAD-I patients or in LFA-1–deficient mice (which exhibit the LAD-I periodontal phenotype) was associated with excessive production of the inflammatory cytokine IL-17, mostly from T cells. Local treatment with antibodies to IL-17 in LFA-1–deficient mice blocked inflammatory periodontal bone loss and reduced the total bacterial burden. These findings suggest that IL-17–targeted therapy for periodontitis might be effective in LAD-I patients, which would clearly be a reason to smile.

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