PMID- 17919493
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20081121
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 133
IP  - 4
DP  - 2007 Oct
TI  - Evidence for the role of interferon-alfa production by dendritic cells in the Th1 
      response in celiac disease.
PG  - 1175-87
AB  - 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.
FAU - Di Sabatino, Antonio
AU  - Di Sabatino A
AD  - Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and 
      the London School of Medicine and Dentistry, London, United Kingdom.
FAU - Pickard, Karen M
AU  - Pickard KM
FAU - Gordon, John N
AU  - Gordon JN
FAU - Salvati, Virginia
AU  - Salvati V
FAU - Mazzarella, Giuseppe
AU  - Mazzarella G
FAU - Beattie, Robert M
AU  - Beattie RM
FAU - Vossenkaemper, Anna
AU  - Vossenkaemper A
FAU - Rovedatti, Laura
AU  - Rovedatti L
FAU - Leakey, Nicholas A B
AU  - Leakey NA
FAU - Croft, Nicholas M
AU  - Croft NM
FAU - Troncone, Riccardo
AU  - Troncone R
FAU - Corazza, Gino R
AU  - Corazza GR
FAU - Stagg, Andrew J
AU  - Stagg AJ
FAU - Monteleone, Giovanni
AU  - Monteleone G
FAU - MacDonald, Thomas T
AU  - MacDonald TT
LA  - eng
PT  - Journal Article
DEP - 20070814
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukins)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 8002-80-0 (Glutens)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-90-3 (Gliadin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
SB  - IM
MH  - Antibodies
MH  - Antigens, CD/analysis
MH  - Case-Control Studies
MH  - Celiac Disease/diet therapy/genetics/immunology/*metabolism
MH  - Cell Differentiation
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/analysis
MH  - Dendritic Cells/immunology/*metabolism
MH  - Diet, Protein-Restricted
MH  - Flow Cytometry
MH  - Gliadin/immunology
MH  - Glutens/*immunology
MH  - Humans
MH  - *Immunity, Cellular
MH  - *Immunity, Mucosal
MH  - Interferon-alpha/genetics/immunology/*metabolism
MH  - Interferon-gamma/genetics/metabolism
MH  - Interleukins/genetics/metabolism
MH  - Intestinal Mucosa/enzymology/immunology/*metabolism
MH  - Microscopy, Confocal
MH  - Peptide Fragments/immunology
MH  - Phenotype
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Th1 Cells/immunology/*metabolism
MH  - Tissue Culture Techniques
MH  - Transforming Growth Factor beta/genetics/metabolism
EDAT- 2007/10/09 09:00
MHDA- 2007/10/27 09:00
CRDT- 2007/10/09 09:00
PHST- 2006/07/24 00:00 [received]
PHST- 2007/06/14 00:00 [accepted]
PHST- 2007/10/09 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2007/10/09 09:00 [entrez]
AID - S0016-5085(07)01475-8 [pii]
AID - 10.1053/j.gastro.2007.08.018 [doi]
PST - ppublish
SO  - Gastroenterology. 2007 Oct;133(4):1175-87. doi: 10.1053/j.gastro.2007.08.018. 
      Epub 2007 Aug 14.