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Unravelling the pathogenesis of inflammatory bowel disease
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TLDR
Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation as mentioned in this paper, which have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis.Abstract:
Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.read more
Citations
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Gut Microbiota in Health and Disease
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Microbial Influences in Inflammatory Bowel Diseases
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The global burden of IBD: from 2015 to 2025
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Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease
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A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells
Ken Cadwell,John Y. Liu,Sarah L. Brown,Hiroyuki Miyoshi,Joy Loh,Jochen K. Lennerz,Chieko Kishi,Wumesh Kc,Javier A. Carrero,Steven C. Hunt,Christian D. Stone,Elizabeth M. Brunt,Ramnik J. Xavier,Barry P. Sleckman,Ellen Li,Noboru Mizushima,Thaddeus S. Stappenbeck,Herbert W. Virgin +17 more
TL;DR: ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn’s disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
References
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Journal Article
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
TL;DR: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished.
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
The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
Ivaylo I. Ivanov,Brent S. McKenzie,Liang Zhou,Carlos E. Tadokoro,Alice Lepelley,Juan J. Lafaille,Daniel J. Cua,Dan R. Littman +7 more
TL;DR: It is shown that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage of proinflammatory T helper cells and its potential as a therapeutic target in inflammatory diseases is highlighted.
Journal ArticleDOI
Metagenomic Analysis of the Human Distal Gut Microbiome
Steven R. Gill,Mihai Pop,Robert T. DeBoy,Paul B. Eckburg,Paul B. Eckburg,Peter J. Turnbaugh,Buck S. Samuel,Jeffrey I. Gordon,David A. Relman,David A. Relman,Claire M. Fraser-Liggett,Karen E. Nelson +11 more
TL;DR: Using metabolic function analyses of identified genes, the human genome is compared with the average content of previously sequenced microbial genomes and humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.
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