Journal ArticleDOI
The immunological and genetic basis of inflammatory bowel disease.
G. Bouma,G. Bouma,Warren Strober +2 more
TLDR
The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease.Abstract:
The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy.read more
Citations
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The gut microbiota shapes intestinal immune responses during health and disease
TL;DR: Findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut are discussed, and the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms is raised.
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Gut Microbiota in Health and Disease
TL;DR: The advances in modeling and analysis of gut microbiota will further the authors' knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.
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Transforming growth factor-beta regulation of immune responses.
TL;DR: This review highlights the findings that have advanced the understanding of TGF-beta in the immune system and in disease.
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The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation
TL;DR: The effector cytokines of Th17 cells mediate the crucial crosstalk between immune system and tissues, and play indispensable roles in tissue immunity.
Journal ArticleDOI
Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis.
TL;DR: These studies indicate that Crohn's disease and ulcerative colitis are heterogeneous diseases characterized by various genetic abnormalities that lead to overly aggressive T-cell responses to a subset of commensal enteric bacteria.
References
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Control of Regulatory T Cell Development by the Transcription Factor Foxp3
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
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Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
Journal ArticleDOI
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
Journal ArticleDOI
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Yasunori Ogura,Denise K. Bonen,Naohiro Inohara,Dan L. Nicolae,Felicia F. Chen,Richard Ramos,Heidi M. Britton,Thomas M. Moran,Reda Karaliuskas,Richard H. Duerr,Jean-Paul Achkar,Steven R. Brant,Theodore M. Bayless,Barbara S. Kirschner,Stephen B. Hanauer,Gabriel Núñez,Judy H. Cho +16 more
TL;DR: It is shown that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease, and a link between an innate immune response to bacterial components and development of disease is suggested.
Journal ArticleDOI
Interleukin-10-deficient mice develop chronic enterocolitis
TL;DR: The results indicate that the bowel inflammation in the mutants originates from uncontrolled immune responses stimulated by enteric antigens and that IL-10 is an essential immunoregulator in the intestinal tract.
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