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Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease.
Gastroenterology. 2007 Oct; 133(4):1175-87.G

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.

Authors+Show Affiliations

Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17919493

Citation

Di Sabatino, Antonio, et al. "Evidence for the Role of Interferon-alfa Production By Dendritic Cells in the Th1 Response in Celiac Disease." Gastroenterology, vol. 133, no. 4, 2007, pp. 1175-87.
Di Sabatino A, Pickard KM, Gordon JN, et al. Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology. 2007;133(4):1175-87.
Di Sabatino, A., Pickard, K. M., Gordon, J. N., Salvati, V., Mazzarella, G., Beattie, R. M., Vossenkaemper, A., Rovedatti, L., Leakey, N. A., Croft, N. M., Troncone, R., Corazza, G. R., Stagg, A. J., Monteleone, G., & MacDonald, T. T. (2007). Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology, 133(4), 1175-87.
Di Sabatino A, et al. Evidence for the Role of Interferon-alfa Production By Dendritic Cells in the Th1 Response in Celiac Disease. Gastroenterology. 2007;133(4):1175-87. PubMed PMID: 17919493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. AU - Di Sabatino,Antonio, AU - Pickard,Karen M, AU - Gordon,John N, AU - Salvati,Virginia, AU - Mazzarella,Giuseppe, AU - Beattie,Robert M, AU - Vossenkaemper,Anna, AU - Rovedatti,Laura, AU - Leakey,Nicholas A B, AU - Croft,Nicholas M, AU - Troncone,Riccardo, AU - Corazza,Gino R, AU - Stagg,Andrew J, AU - Monteleone,Giovanni, AU - MacDonald,Thomas T, Y1 - 2007/08/14/ PY - 2006/07/24/received PY - 2007/06/14/accepted PY - 2007/10/9/pubmed PY - 2007/10/27/medline PY - 2007/10/9/entrez SP - 1175 EP - 87 JF - Gastroenterology JO - Gastroenterology VL - 133 IS - 4 N2 - 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. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/17919493/Evidence_for_the_role_of_interferon_alfa_production_by_dendritic_cells_in_the_Th1_response_in_celiac_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)01475-8 DB - PRIME DP - Unbound Medicine ER -