Evidence for the Role of Interferon-alfa Production by Dendritic Cells in the Th1 Response in Celiac Disease

Antonio Di Sabatino, Karen M. Pickard, John N. Gordon, Virginia Salvati, Giuseppe Mazzarella, Robert M. Beattie, Anna Vossenkaemper, Laura Rovedatti, Nicholas A B Leakey, Nicholas M. Croft, Riccardo Troncone, Gino R. Corazza, Andrew J. Stagg, Giovanni Monteleone, Thomas T. MacDonald

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: Dendritic cells (DCs) play a crucial role in immune responses by controlling the extent and type of T-cell response to antigen. Celiac disease is a condition in which T-cell immunity to gluten plays an important pathogenic role, yet information on DCs is scant. We examined mucosal DCs in celiac disease in terms of phenotype, activation/maturation state, cytokine production, and function. Methods: Mucosal DCs from 48 celiacs and 30 controls were investigated by flow cytometry. In situ distribution of DCs was analyzed by confocal microscopy. Interferon (IFN)-alfa, interleukin (IL)-4, IL-5, IL-12p35, IL-12p40, IL-18, IL-23p19, IL-27, and transforming growth factor-β transcripts were measured by real-time reverse-transcription polymerase chain reaction in sorted DCs. DC expression of IL-6, IL-12p40, and IL-10 was assessed by intracellular cytokine staining. The effect of IFN-alfa and IL-18 blockade on the gluten-induced IFN-γ response in celiac biopsy specimens grown ex vivo also was investigated. Results: Mucosal DCs were increased in untreated, but not treated, celiacs. The majority of them were plasmacytoid with higher levels of maturation (CD83) and activation (CD80/CD86) markers. Higher transcripts of Th1 relevant cytokines, such as IFN-alfa, IL-18, and IL-23p19, were produced by celiac DCs, but because IL-12p40 was undetectable, a role for IL-23 is unlikely. Intracellular cytokine staining of celiac DCs showed higher IL-6, but lower IL-10 expression, and confirmed the lack of IL-12p40. Blocking IFN-alfa inhibited IFN-γ transcripts in ex vivo organ culture of celiac biopsy specimens challenged with gluten. Conclusions: These data suggest that IFN-alfa-producing DCs contribute to the Th1 response in celiac disease.

Original languageEnglish
Pages (from-to)1175-1187
Number of pages13
JournalGastroenterology
Volume133
Issue number4
DOIs
Publication statusPublished - Oct 2007

ASJC Scopus subject areas

  • Gastroenterology

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