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Celiac Disease: HELP
Articles by Valérie Abadie
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, V. Abadie wrote the following 8 articles about Celiac Disease.
 
+ Citations + Abstracts
1 Review IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction. 2015

Jabri, Bana / Abadie, Valérie. ·Departments of Medicine, Pathology and Pediatrics, University of Chicago, Knapp Center for Biomedical Discovery (KCBD), Chicago, Illinois 60637, USA. · Department of Microbiology, Infectious Diseases, and Immunology, University of Montreal, and the Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada. ·Nat Rev Immunol · Pubmed #26567920.

ABSTRACT: In this Opinion article, we discuss the function of tissues as a crucial checkpoint for the regulation of effector T cell responses, and the notion that interleukin-15 (IL-15) functions as a danger molecule that communicates to the immune system that the tissue is under attack and poises it to mediate tissue destruction. More specifically, we propose that expression of IL-15 in tissues promotes T helper 1 cell-mediated immunity and provides co-stimulatory signals to effector cytotoxic T cells to exert their effector functions and drive tissue destruction. Therefore, we think that IL-15 contributes to tissue protection by promoting the elimination of infected cells but that when its expression is chronically dysregulated, it can promote the development of complex T cell-mediated disorders associated with tissue destruction, such as coeliac disease and type 1 diabetes.

2 Review IL-15: a central regulator of celiac disease immunopathology. 2014

Abadie, Valérie / Jabri, Bana. ·Sainte-Justine Hospital Research Center, Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Montreal, Canada. ·Immunol Rev · Pubmed #24942692.

ABSTRACT: Interleukin-15 (IL-15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL-15 upregulation has been reported in many organ-specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL-15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL-15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL-15 with regard to the main immunological processes involved in the pathogenesis of celiac disease.

3 Review Intraepithelial lymphocytes in celiac disease immunopathology. 2012

Abadie, Valérie / Discepolo, Valentina / Jabri, Bana. ·Sainte-Justine Hospital Research Centre, Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada. valerie.abadie@umontreal.ca ·Semin Immunopathol · Pubmed #22660791.

ABSTRACT: Celiac disease is a T cell-mediated immune disorder induced by dietary gluten that is characterized by the development of an inflammatory anti-gluten CD4 T cell response, anti-gluten antibodies, and autoantibodies against tissue transglutaminase 2 and the activation of intraepithelial lymphocytes (IELs) leading to the destruction of the intestinal epithelium. Intraepithelial lymphocytes represent a heterogeneous population of T cells composed mainly of cytotoxic CD8 T cells residing within the epithelial layer, whose main role is to maintain the integrity of the epithelium by eliminating infected cells and promoting epithelial repair. Dysregulated activation of IELs is a hallmark of CD and is critically involved in epithelial cell destruction and the subsequent development of villous atrophy. In this review, we compare and contrast the phenotype and function of human and mouse small intestinal IELs under physiological conditions. Furthermore, we discuss how conditions of epithelial distress associated with overexpression of IL-15 and non-classical MHC class I molecules induce cytotoxic IELs to become licensed killer cells that upregulate activating NKG2D and CD94/NKG2C natural killer receptors, acquiring lymphokine killer activity. Pathways leading to dysregulated IEL activation could eventually be targeted to prevent villous atrophy and treat patients who respond poorly to gluten-free diet.

4 Review Integration of genetic and immunological insights into a model of celiac disease pathogenesis. 2011

Abadie, Valérie / Sollid, Ludvig M / Barreiro, Luis B / Jabri, Bana. ·Department of Medicine, University of Chicago, Illinois 60637, USA. ·Annu Rev Immunol · Pubmed #21219178.

ABSTRACT: Celiac disease (CD) is a gluten-sensitive enteropathy that develops in genetically susceptible individuals by exposure to cereal gluten proteins. This review integrates insights from immunological studies with results of recent genetic genome-wide association studies into a disease model. Genetic data, among others, suggest that viral infections are implicated and that natural killer effector pathways are important in the pathogenesis of CD, but most prominently these data converge with existing immunological findings that CD is primarily a T cell-mediated immune disorder in which CD4(+) T cells that recognize gluten peptides in the context of major histocompatibility class II molecules play a central role. Comparison of genetic pathways as well as genetic susceptibility loci between CD and other autoimmune and inflammatory disorders reveals that CD bears stronger resemblance to T cell-mediated organ-specific autoimmune than to inflammatory diseases. Finally, we present evidence suggesting that the high prevalence of CD in modern societies may be the by-product of past selection for increased immune responses to combat infections in populations in which agriculture and cereals were introduced early on in the post-Neolithic period.

5 Article Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. 2017

Bouziat, Romain / Hinterleitner, Reinhard / Brown, Judy J / Stencel-Baerenwald, Jennifer E / Ikizler, Mine / Mayassi, Toufic / Meisel, Marlies / Kim, Sangman M / Discepolo, Valentina / Pruijssers, Andrea J / Ernest, Jordan D / Iskarpatyoti, Jason A / Costes, Léa M M / Lawrence, Ian / Palanski, Brad A / Varma, Mukund / Zurenski, Matthew A / Khomandiak, Solomiia / McAllister, Nicole / Aravamudhan, Pavithra / Boehme, Karl W / Hu, Fengling / Samsom, Janneke N / Reinecker, Hans-Christian / Kupfer, Sonia S / Guandalini, Stefano / Semrad, Carol E / Abadie, Valérie / Khosla, Chaitan / Barreiro, Luis B / Xavier, Ramnik J / Ng, Aylwin / Dermody, Terence S / Jabri, Bana. ·Department of Medicine, University of Chicago, Chicago, IL, USA. · Committee on Immunology, University of Chicago, Chicago, IL, USA. · Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. · Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, and CeInGe-Biotecnologie Avanzate, Naples, Italy. · Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, Netherlands. · Department of Chemistry, Stanford University, Stanford, CA, USA. · Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Broad Institute of MIT and Harvard University, Cambridge, MA, USA. · University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA. · Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA. · Department of Microbiology, Infectiology, and Immunology, University of Montreal, and the Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, Quebec, Canada. · Department of Chemical Engineering, Stanford University, Stanford, CA, USA. · Stanford ChEM-H, Stanford University, Stanford, California, USA. · Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada. · Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu. · Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Medicine, University of Chicago, Chicago, IL, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu. · Department of Pathology, University of Chicago, Chicago, IL, USA. ·Science · Pubmed #28386004.

ABSTRACT: Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T

6 Article Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease. 2015

Tang, Fangming / Sally, Benjamin / Lesko, Kathryn / Discepolo, Valentina / Abadie, Valerie / Ciszewski, Cezary / Semrad, Carol / Guandalini, Stefano / Kupfer, Sonia S / Jabri, Bana. ·Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637. · Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 European Laboratory for the Investigation of Food-Induced Disorders (ELFID), Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80138 Naples, Italy. · Sainte-Justine Hospital Research Center, Department of Microbiology, Infectiology, and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada. · Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 Department of Medicine, University of Chicago Celiac Disease Center, and Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637 bjabri@bsd.uchicago.edu. ·J Exp Med · Pubmed #26304964.

ABSTRACT: Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor-independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell-mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated.

7 Article Distinct and Synergistic Contributions of Epithelial Stress and Adaptive Immunity to Functions of Intraepithelial Killer Cells and Active Celiac Disease. 2015

Setty, Mala / Discepolo, Valentina / Abadie, Valérie / Kamhawi, Sarah / Mayassi, Toufic / Kent, Andrew / Ciszewski, Cezary / Maglio, Maria / Kistner, Emily / Bhagat, Govind / Semrad, Carol / Kupfer, Sonia S / Green, Peter H / Guandalini, Stefano / Troncone, Riccardo / Murray, Joseph A / Turner, Jerrold R / Jabri, Bana. ·Department of Pediatrics, University of Chicago, Chicago, Illinois. · Department of Pediatrics, University of Chicago, Chicago, Illinois; European Laboratory for the Investigation of Food-Induced Disorders, Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy; Department of Medicine, University of Chicago, Chicago, Illinois; CEINGE-Biotecnologie Avanzate, Naples, Italy. · Sainte-Justine Hospital Research Center, Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, University of Montreal, Montreal, Canada. · Department of Medicine, University of Chicago, Chicago, Illinois. · European Laboratory for the Investigation of Food-Induced Disorders, Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy. · Department of Health Studies, University of Chicago, Chicago, Illinois. · Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York. · Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York, New York. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota. · Department of Medicine, University of Chicago, Chicago, Illinois; Department of Pathology, University of Chicago, Chicago, Illinois. Electronic address: jturner@bsd.uchicago.edu. · Department of Pediatrics, University of Chicago, Chicago, Illinois; Department of Medicine, University of Chicago, Chicago, Illinois. Electronic address: bjabri@bsd.uchicago.edu. ·Gastroenterology · Pubmed #26001928.

ABSTRACT: BACKGROUND & AIMS: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy. METHODS: We collected blood and intestinal biopsy specimens from 268 patients at tertiary medical centers in the United States and Italy from 2004 to 2012. All subjects had normal small intestinal histology. Study groups included healthy individuals with no family history of celiac disease or antibodies against tissue transglutaminase 2 (controls), healthy family members of patients with celiac disease, and potential celiac disease patients. Intraepithelial cytotoxic T cells were isolated and levels of inhibitory and activating natural killer (NK) cells were measured by flow cytometry. Levels of heat shock protein (HSP) and interleukin 15 were measured by immunohistochemistry, and ultrastructural alterations in intestinal epithelial cells (IECs) were assessed by electron microscopy. RESULTS: IECs from subjects with a family history of celiac disease, but not from subjects who already had immunity to gluten, expressed higher levels of HS27, HSP70, and interleukin-15 than controls; their IECs also had ultrastructural alterations. Intraepithelial cytotoxic T cells from relatives of patients with celiac disease expressed higher levels of activating NK receptors than cells from controls, although at lower levels than patients with active celiac disease, and without loss of inhibitory receptors for NK cells. Intraepithelial cytotoxic T cells from potential celiac disease patients failed to up-regulate activating NK receptors. CONCLUSIONS: A significant subset of healthy family members of patients with celiac disease with normal intestinal architecture had epithelial alterations, detectable by immunohistochemistry and electron microscopy. The adaptive immune response to gluten appears to act in synergy with epithelial stress to allow intraepithelial cytotoxic T cells to kill epithelial cells and induce villous atrophy in patients with active celiac disease.

8 Article Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. 2011

DePaolo, R W / Abadie, V / Tang, F / Fehlner-Peach, H / Hall, J A / Wang, W / Marietta, E V / Kasarda, D D / Waldmann, T A / Murray, J A / Semrad, C / Kupfer, S S / Belkaid, Y / Guandalini, S / Jabri, B. ·Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. ·Nature · Pubmed #21307853.

ABSTRACT: Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.