Abstract
The airway epithelium is an important barrier interface for the lungs and plays a key role in various lung inflammatory disorders. MS4A8B, a member of the MS4A (membrane-spanning, 4 domains, subfamily A) family, contains a putative immunoreceptor tyrosine-based inhibitory motif (ITIM) and we have previously shown that MS4A8B is expressed on the cilia of airway epithelial cells. Our study aimed to determine the expression and function of MS4A8B in the human airways and to clarify its role in lung inflammatory disorders.
Real-time PCR was performed on healthy and COPD primary bronchial epithelial cells (PBECs) grown at an air-liquid interface (ALI) to examine differences in MS4A8B expression. MS4A8B, and an ITIM mutant form, were transfected into the BEAS-2B and HEK293 cell lines to examine its effects on cellular function and signaling.
MS4A8B gene expression increased over time as PBECs underwent complete mucociliary differentiation. Compared to healthy donors, MS4A8B gene expression was reduced in ALI cultured PBECs obtained from COPD patients. Transfected BEAS-2B cells stably expressing MS4A8B showed a reduced proinflammatory cytokine production and enhanced proliferation that was reversed by tyrosine mutation of the proteins ITIM motif. In signaling studies, MS4A8B was shown to be tyrosine phosphorylated in transfected HEK293 cells following sodium pervanadate treatment with this effect being lost upon MS4A8B ITIM mutation.
Our combined data suggests that MS4A8B is an important control mechanism in the airway epithelium and that its ITIM motif is critical for this effect. The loss of MS4A8B expression in airway disease such as COPD may thus enhance airway inflammation and worsen disease.
- Copyright ©ERS 2015