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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease.
Anno di pubblicazione: 2007
Autori: Di Sabatino A, Pickard KM, Gordon JN, Salvati V, Mazzarella G, Beattie RM, Vossenkaemper A, Rovedatti L, Leakey NA, Croft NM, Troncone R, Corazza GR, Stagg AJ, Monteleone G, MacDonald TT.
Affiliazioni autori: *Centres for Infectious Disease and #Gastroenterology, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom; ?Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, United Kingdom; §Department of Pediatrics, University Federico II of Naples, Naples, Italy; Institute of Food Science, Consiglio Nazionale delle Ricerche, Avellino, Italy; ¶Pediatric Medical Unit, Southampton General Hospital, Southampton, United Kingdom; **First Department of Medicine, Centro per lo Studio e la Cura della Malattia Celiaca, Fondazione Instituto de Ricovero e Cura Carattere Scientifico Policlinico S. Matteo, University of Pavia, Pavia, Italy; ??Antigen Presentation Research Group, Imperial College, London, United Kindom; and the §§Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Universitą Tor Vergata, Rome, Italy
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-beta 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-gamma 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-gamma 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.
Lingua abstract: inglese
Pagine da: 1175
Pagine a: 1187
Numero volume: 133
Indicizzato da: ISI Web of Science (WOS) 
Altre informazioni: 4
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