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, IL12p40, 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.
Di Sabatino A., P.K. (2007). Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. GASTROENTEROLOGY, 133(4), 1175-1187.
|Tipologia:||Articolo su rivista|
|Citazione:||Di Sabatino A., P.K. (2007). Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. GASTROENTEROLOGY, 133(4), 1175-1187.|
|Altre informazioni significative:||13|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1053/j.gastro.2007.08.018|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2007|
|Titolo:||Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease|
|Autori:||Di Sabatino A., Pickard K.M., Gordon J.N., Salvati V., Mazzarella G., Beattie R.M., Vossenkaemper A., Rovedatti L., Leakey N.A.B., Croft N.M., Troncone R., Corazza G.R., Stagg A.J., Monteleone G., MacDonald T.T.|
|Appare nelle tipologie:||01 - Articolo su rivista|