Identification of a novel immunomodulatory gliadin peptide that causes interleukin-8 release in a chemokine receptor CXCR3-dependent manner only in patients with coeliac disease
Version of Record online: 23 NOV 2010
© 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd
Volume 132, Issue 3, pages 432–440, March 2011
How to Cite
Lammers, K. M., Khandelwal, S., Chaudhry, F., Kryszak, D., Puppa, E. L., Casolaro, V. and Fasano, A. (2011), Identification of a novel immunomodulatory gliadin peptide that causes interleukin-8 release in a chemokine receptor CXCR3-dependent manner only in patients with coeliac disease. Immunology, 132: 432–440. doi: 10.1111/j.1365-2567.2010.03378.x
- Issue online: 1 FEB 2011
- Version of Record online: 23 NOV 2010
- Received 17 August 2010; revised 24 September 2010; accepted 11 October 2010.
- coeliac disease;
- peripheral blood mononuclear cells
The autoimmune enteropathy, coeliac disease (CD), is triggered by ingestion of gluten-containing grains. We recently reported that the chemokine receptor CXCR3 serves as a receptor for specific gliadin peptides that cause zonulin release and subsequent increase in intestinal permeability. To explore the role of CXCR3 in the immune response to gliadin, peripheral blood mononuclear cells from both patients with CD and healthy controls were incubated with either pepsin-trypsin-digested gliadin or 11 α-gliadin synthetic peptides in the presence or absence of a blocking anti-CXCR3 monoclonal antibody. Supernatants were analysed for interleukin-6 (IL-6), IL-8, IL-10, IL-13, IP-10 (CXCL10), tumour necrosis factor-α and interferon-γ. Gliadin broadly induced cytokine production irrespective of the clinical condition. However, IL-8 production occurred only in a subgroup of individuals and cells of the phagocytic lineage were the main source. Induction of IL-8 was reproduced by one of a comprehensive panel of synthetic α-gliadin peptides and was abrogated when CXCR3 was blocked before stimulation with either gliadin or this peptide in the CD group but not in the control group, suggesting that gliadin-induced IL-8 production was CXCR3-dependent gliadin induced IL-8 production only in CD.