Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease

Monteleone, Giovanni; Pender, Sylvia L.F.; Alstead, Elspeth; Hauer, A.; Lionetti, Paolo; MacDonald, Thomas T.

doi:10.1136/gut.48.3.425

Cited by 132 publications

(111 citation statements)

References 31 publications

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“…Celiac disease is associated with a predominantly Th1 or Th0 type of cytokine response in established disease (44). The cytokine profile in these mice resembles that of a regulatory phenotype and thus differs from that seen in established celiac disease.…”

Section: Discussionmentioning

confidence: 99%

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Black¹,

Murray

David³

2002

The Journal of Immunology

137

107

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We have investigated the genetic basis of the immune response to dietary gluten in HCD4/DQ8 and HCD4/DQ6 double transgenic mice. Mice were immunized with gluten i.p. or individual peptides s.c. and spleen or draining lymph node T cells were challenged in vitro. Strong proliferative responses to gluten were seen in the HCD4/DQ8 mice, whereas the HCD4/DQ6 mice responded to gluten poorly. A series of overlapping peptides spanning gliadin were synthesized. The HCD4/DQ8 mice reacted to many of the individual peptides of gliadin, while the HCD4/DQ6 mice were relatively unresponsive. T cells isolated from HCD4/DQ8 mice also responded well to modified (deamidated) versions of the gliadin peptides, whereas HCD4DQ6 mice did not. The T cell response to gluten was CD4 dependent and DQ restricted and led to the production of cytokines IL-6, TGF-β, and IL-10. Finally, intestinal lymphocytes isolated from gluten-fed HCD4/DQ8 mice displayed an activated phenotype. These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease.

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Section: Discussionmentioning

confidence: 99%

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Black¹,

Murray

David³

2002

The Journal of Immunology

137

107

View full text Add to dashboard Cite

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“…26,27 However, these animals showed a specific up-regulation of IFN-1, similar to that observed in IBS-like states. 28,29 Colonic motor changes after long term exposure to oral OVA are related to an excited-activated state of MMCs. 21 Moreover,…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharides Facilitate Colonic Motor Alterations Associated to the Sensitization to a Luminal Antigen in Rats

Jardí

Aguilera

Vergara

et al. 2015

J Neurogastroenterol Motil

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Background/Aims Enteric dysbiosis is a risk factor for dietary proteins-associated intestinal alterations, contributing to the development of food allergies and the symptomatology of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS). We explored if a dysbiotic-like state, simulated by intraperitoneal administration of bacterial lipopolysaccharides (LPS), facilitates the sensitization to a luminal antigen, ovalbumin (OVA), in rats. Methods Rats were exposed to oral OVA for 1 week, alone or with LPS. Thereafter, colonic histology, goblet cell density, mucosal eosinophils and mucosal mast cell (MMC) and connective tissue mast cell (CTMC) were evaluated. Colonic expression (real-time quantitative polymerase chain reaction) of interleukins, IFN-α1 and integrins was assessed to determine local immune responses. Luminal and wall adhered microbiota were characterized by fluorescence in situ hybridization. Colonic contractility (in vitro) served to assess functional changes associated to OVA and/or LPS. Results Neither OVA nor LPS, alone or combined, lead to structural alterations, except for a reduced goblet cell density in OVA-LPS-treated rats. MMC density was unaffected, while CTMC counts increased within the submucosa of OVA-LPS-treated animals. Marginal immune activation (IFN-α1 up-regulation) was observed in OVA-LPS-treated rats. LPS induced a dysbiotic-like state characterized by decreased luminal bacterial counts, with a specific loss of clostridia. LPS facilitated Clostridium spp. wall adherence, an effect prevented by OVA. Colonic contractility was altered in OVA-LPS-treated animals, showing increased basal activity and enhanced motor responses to OVA. Conclusions Changes in gut microbiota and/or direct effects of LPS might enhance/facilitate local neuroimmune responses to food antigens leading to motor alterations similar to those observed in IBS.

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“…Cette hypothèse rendrait compte à la fois de l'inflammation intestinale et de la fréquence des maladies auto-immunes associées. La perturbation des fonctions de ces lymphocytes T pourrait être détermi-née génétiquement ou être provoquée par des facteurs environnementaux, tels que l'interféron α produit au cours d'infections virales [13]. En induisant la maturation des cellules présentatrices d'antigène et la production d'interféron γ et d'IL-15, celui-ci pourrait favoriser l'apparition de cellules effectrices Th1 aux dépens de la population modulatrice [59,60].…”

Section: Perturbations Des Mécanismes De Tolérance Oraleunclassified

La maladie cœliaque : une maladie auto-immune induite par un antigène alimentaire

Cerf‐Bensussan

Jabrì

2001

Med Sci (Paris)

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L a maladie coeliaque (MC) est une entéropathie induite par les prolamines du blé (gluten) et les protéines apparentées du seigle et de l'orge. La maladie coeliaque est une maladie chronique multifactorielle impliquant des facteurs environnementaux et génétiques. Elle s'apparente moins aux allergies alimentaires qu'aux maladies auto-immunes, auxquelles elle est fréquemment associée. Néanmoins, son expression strictement dépendante d'une expo- 1129La maladie coeliaque : une maladie auto-immune induite par un antigène alimentaire La maladie coeliaque est une entéropathie auto-immune induite par un antigène alimentaire, la gliadine, chez des sujets génétiquement prédisposés. Un schéma pathogé-nique intégrant la liaison génétique aux molécules HLA et l'enzyme cible des auto-anticorps, la transglutaminase, fait jouer un rôle central aux lymphocytes T CD4 + du chorion qui répondent à certains peptides de la gliadine présentés par les molécules HLA-DQ2/8 après désamidation par la transglutaminase. La production des auto-anticorps serait secondaire à la reconnaissance par le système immunitaire de la transglutaminase complexée à la gliadine. Le méca-nisme de l'hyperplasie lymphoïde intra-épithéliale, caracté-ristique de la maladie et à l'origine de complications malignes, n'est pas élucidé. Elle pourrait être déclenchée par un peptide toxique de la gliadine distinct des peptides stimulant les lymphocytes T CD4 + , et être secondaire à l'activation de récepteurs de l'immunité innée sur les lymphocytes intra-épithéliaux et à la production de cytokines par les entérocytes modifiés par l'inflammation ou le stress. La poursuite du démembrement des facteurs génétiques et environnementaux s'avère nécessaire pour élucider les mécanismes enclenchant la réaction immune anormale à la gliadine, comprendre la très grande hétérogénéité clinique et histologique de la maladie et peut-être à terme proposer une alternative au régime sans gluten très contraignant. médecine/sciences 2001 ; 17 : 1129-38 m/s n°11, vol. 17, novembre 2001 Nadine Cerf-Bensussan Bana JabriArticle disponible sur le site

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Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease

Cited by 132 publications

References 31 publications

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Lipopolysaccharides Facilitate Colonic Motor Alterations Associated to the Sensitization to a Luminal Antigen in Rats

La maladie cœliaque : une maladie auto-immune induite par un antigène alimentaire

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