NK Cell Activating Receptor Ligand Expression in Lymphangioleiomyomatosis is Associated with Lung Function Decline

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2016 Oct 14

PMID 27734028

Citations 10

Authors

Andrew R Osterburg

Rebecca L Nelson

Benyamin Z Yaniv

Rachel Foot

Walter Rf Donica

Madison A Nashu

Huan Liu

Kathryn A Wikenheiser-Brokamp

Joel Moss

Nishant Gupta

Francis X McCormack

Michael T Borchers

Affiliations

Soon will be listed here.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules. We found elevated soluble serum ULBP2 (mean = 575 pg/ml ± 142) in 50 of 100 subjects and ULBP3 in 30 of 100 (mean = 8,300 pg/ml ± 1,515) subjects. LAM patients had fewer circulating NKG2D NK cells and decreased NKG2D surface expression. Lung function decline was associated with soluble NKG2D ligand (sNKG2DL) detection. The greatest rate of decline forced expiratory volume in 1 second (FEV, -124 ± 30 ml/year) in the 48 months after enrollment (NHLBI LAM Registry) occurred in patients expressing both ULBP2 and ULBP3, whereas patients with undetectable sNKG2DL levels had the lowest rate of FEV decline (-32.7 ± 10 ml/year). These data suggest a role for NK cells, sNKG2DL, and the innate immune system in LAM pathogenesis.

Citing Articles

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