Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.
Yasunori Ogura,S. Lala,Wei Xin,Elizabeth Smith,Theresa A Dowds,Felicia F. Chen,Ellen M. Zimmermann,Maria Tretiakova,Judy H. Cho,John Hart,Joel K. Greenson,Satish Keshav,Gabriel Núñez +12 more
TLDR
A role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria is suggested and a plausible mechanism to explain the selective association of N OD2 mutations with ileal disease is suggested.Abstract:
Background and aims: Genetic variation in NOD2 has been associated with susceptibility to Crohn’s disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls.
Patients and methods: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method.
Results: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls.
Conclusions: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.read more
Citations
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Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology
Mark S. Silverberg,Jack Satsangi,Tariq Ahmad,Ian D. Arnott,Charles N. Bernstein,Steven R. Brant,Renzo Caprilli,Jean-Frederic Colombel,Christoph Gasche,Karel Geboes,Derek P. Jewell,Amir Karban,Edward V. Loftus,A. Salvador Peña,Robert H. Riddell,David B. Sachar,Stefan Schreiber,A. Hillary Steinhart,Stephan R. Targan,Severine Vermeire,Bryan F. Warren +20 more
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Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.
Koichi Kobayashi,Mathias Chamaillard,Yasunori Ogura,Octavian Henegariu,Naohiro Inohara,Gabriel Núñez,Richard A. Flavell +6 more
TL;DR: It is shown that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod1-deficient mice, providing a possible mechanism for Nod 2 mutations in CD.
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References
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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
Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.
Stephen E. Girardin,Ivo G. Boneca,Jérôme Viala,Mathias Chamaillard,Agnès Labigne,Gilles Thomas,Dana J. Philpott,Philippe J. Sansonetti +7 more
TL;DR: It is shown here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptIDoglycan motif common to all bacteria.
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Inflammatory bowel disease: Etiology and pathogenesis
TL;DR: No single agent or distinct mechanism is the sine qua non motive that explains all aspects of IBD, and several distinguishing factors are likely necessary to result in either CD or UC; this review will attempt to discuss those that currently appear important.
Journal Article
A New Mouse Myeloma Cell Line that Has Lost Immunoglobulin Expression but Permits the Construction of Antibody-Secreting Hybrid Cell Lines
TL;DR: A subclone of the mouse myeloma cell line P3-X63-Ag8 that does not express immunoglobulin heavy or light chains is isolated and can be used for efficient fusion with antibody-forming cells to obtain hybrid cell lines producing pure monoclonal antibodies.
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