Allergy Asthma Immunol Res.  2012 Sep;4(5):295-304. 10.4168/aair.2012.4.5.295.

TLR4, 5, and 9 Agonists Inhibit Murine Airway Invariant Natural Killer T Cells in an IL-12-Dependent Manner

Affiliations
  • 1Department of Allergy, Asthma and Clinical Immunology, Chonnam National University Medical School, Gwangju, Korea. yikoh@chonnam.ac.kr
  • 2Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea.

Abstract

PURPOSE
Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma.
METHODS
Because increased alpha-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, alpha-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naive BALB/c mice. Intracellular IL-4 and IFN-gamma were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined.
RESULTS
Intranasal administration of LPS, flagellin, or CpG reduced development of alpha-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-gamma from alpha-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb.
CONCLUSIONS
TLR4, 5, and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists.

Keyword

CpG; flagellin; lipopolysaccharide; natural killer T cells

MeSH Terms

Administration, Intranasal
Animals
Asthma
Bronchoalveolar Lavage
Cytokines
Eosinophils
Flagellin
Galactosylceramides
Humans
Inflammation
Interleukin-12
Interleukin-4
Mice
Natural Killer T-Cells
Spleen
Cytokines
Flagellin
Galactosylceramides
Interleukin-12
Interleukin-4
Full Text Links
  • AAIR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error