Low sphingosine-1-phosphate impairs lung dendritic cells in cystic fibrosis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Histocompatibility Antigens Class II
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout

MeSH Major

  • Dendritic Cells
  • Lung
  • Lysophospholipids
  • Sphingosine

abstract

  • Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) leads to chronic inflammation and infection of the respiratory tract. The role of CFTR for cells of the pulmonary immune system is only partly understood. The present study analyzes the phenotype and immune stimulatory capacity of lung dendritic cells (DCs) from CFTR knockout (CF) mice. Total numbers of conventional DCs, plasmacytoid DCs, and CD103-positive DCs were lower in CF mice compared with wild-type (WT) control mice, as was the expression of major histocompatibility complex class II molecules (MHCII), CD40, and CD86. After pulmonary infection with respiratory syncytial virus, DC numbers increased in WT mice but not in CF mice, and the T cell-stimulatory capacity of CF DCs was impaired. The culture of CF lung DCs with bronchoalveolar lavage fluid (BALF) from WT mice increased the expression of MHCII, CD40, and CD86. The supplementation of CF BALF with sphingosine-1-phosphate (S1P), a mediator of immune cell migration and activation that is decreased in CF BALF, rescued the reduced expression of MHCII and CD40 in WT lung DCs and human blood DCs. These findings suggest that DCs are impaired in the CF lung, and that altered S1P affects lung DC function. These findings provide a novel link between defective CFTR and pulmonary innate immune dysfunction in CF.

publication date

  • February 2013

has subject area

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Dendritic Cells
  • Histocompatibility Antigens Class II
  • Lung
  • Lymphocyte Activation
  • Lysophospholipids
  • Mice
  • Mice, Knockout
  • Sphingosine

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3604068

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2012-0021OC

PubMed ID

  • 23239501

Additional Document Info

start page

  • 250

end page

  • 257

volume

  • 48

number

  • 2