| Innate signals from Nod2 block respiratory tolerance and program T(H)2-driven allergic inflammation. | |
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MedLine Citation:
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PMID: 21051079 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Airway tolerance is critical for protecting the lung from inflammatory disease driven by allergens. However, factors that disrupt tolerance processes and then lead to susceptibility to developing allergic asthma remain elusive. OBJECTIVE: To investigate whether recognition of bacterial microbial-associated molecular patterns in the lung may result in susceptibility to developing allergic reactions, and to understand the molecular mechanisms by which such triggers block natural tolerance. METHODS: Ligands of intracellular microbial-associated molecular pattern recognition receptors-the nucleotide-binding oligomerization domain (Nod)-like receptors, Nod1 and Nod2-were given intranasally with antigen, and their ability to modulate airway tolerance was analyzed. RESULTS: Intranasal Nod2 ligand rapidly induced lung expression of the innate cytokines thymic stromal lymphopoietin and IL-25, and thymic stromal lymphopoietin promoted expression of OX40 ligand, a T-cell-costimulatory ligand, on lung CD11c(+)CD11b(+) cells and B220(+) cells. Together these 3 molecules blocked the generation of antigen-specific CD4(+)forkhead box protein 3(+) adaptive regulatory T cells and concomitantly drove IL-4-producing CD4 T cells. By altering the regulatory T/T(H)2-cell balance, tolerance was blocked, and sensing of Nod2 ligand resulted in subsequent susceptibility to developing eosinophil-dominated airway inflammation. CONCLUSION: We show that a Nod-like receptor is a novel, previously unrecognized, pathway that adversely links innate and adaptive immunity and leads to allergic disease and asthmatic lung inflammation. |
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Authors:
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Wei Duan; Amit K Mehta; Joao G Magalhaes; Steven F Ziegler; Chen Dong; Dana J Philpott; Michael Croft |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-04 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 126 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-07 Completed Date: 2011-04-05 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1284-93.e10 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylmuramyl-Alanyl-Isoglutamine
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administration & dosage,
pharmacology Allergens / administration & dosage Animals Cells, Cultured Cytokines / biosynthesis, genetics Eosinophilia Hypersensitivity / drug therapy, immunology*, pathology, physiopathology Immune Tolerance / drug effects Immunity, Innate / immunology Interleukin-17 / biosynthesis, genetics Lung / immunology, metabolism*, pathology Mice Mice, Inbred C57BL Nod2 Signaling Adaptor Protein / administration & dosage*, agonists OX40 Ligand / biosynthesis, genetics Signal Transduction / immunology T-Lymphocytes, Regulatory / drug effects, immunology, metabolism*, pathology Th2 Cells / drug effects, immunology, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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AI070535/AI/NIAID NIH HHS; AI071130/AI/NIAID NIH HHS; CA91837/CA/NCI NIH HHS; R01 AR056113-04/AR/NIAMS NIH HHS; R01 CA091837-08/CA/NCI NIH HHS; U19 AI070535-04S17667/AI/NIAID NIH HHS; U19 AI071130-050006/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Allergens; 0/Card15 protein, mouse; 0/Cytokines; 0/IL25 protein, human; 0/Interleukin-17; 0/Nod2 Signaling Adaptor Protein; 0/OX40 Ligand; 0/thymic stromal lymphopoietin; 53678-77-6/Acetylmuramyl-Alanyl-Isoglutamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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