| Inefficient lymph node sensitization during respiratory viral infection promotes IL-17-mediated lung pathology. | |
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MedLine Citation:
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PMID: 20805422 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Development of bronchus-associated lymphoid tissue has been suggested to enhance local antiviral immune responses; however, ectopic lymph node formation often corresponds to chronic inflammatory diseases. These studies investigated the role of ectopic pulmonary lymph nodes upon respiratory syncytial virus (RSV) infection using CCR7-deficient mice, which develop bronchus-associated lymphoid tissue early in life. CCR7(-/-) mice exhibited impaired secondary lymph node formation, enhanced effector T cell responses and pathogenic mucus production in the lung after RSV infection. IL-17 production from CD4 T cells in CCR7(-/-) mice was most remarkably enhanced. Wild-type animals reconstituted with CCR7(-/-) bone marrow recapitulated the pathogenic lung phenotype in CCR7(-/-) mice, whereas CCR7(-/-) animals reconstituted with wild-type bone marrow had normal lymph node development, diminished IL-17 production and reduced lung pathology. Mixed bone marrow chimeras revealed an alteration of immune responses only in CCR7(-/-) T cells, suggesting that impaired trafficking promotes local effector cell generation. Lymphotoxin-α-deficient mice infected with RSV were used to further examine locally induced immune responses and demonstrated increased mucus production and amplified cytokine responses in the lung, especially IL-17. Neutralization of IL-17 in CCR7(-/-) or in lymphotoxin-α-deficient animals specifically inhibited mucus hypersecretion and reduced IL-13. Thus, immune cell trafficking to secondary lymph nodes is necessary for appropriate cytokine responses to RSV as well as modulation of the local environment. |
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Authors:
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Lara E Kallal; Adam J Hartigan; Cory M Hogaboam; Matthew A Schaller; Nicholas W Lukacs |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-30 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-22 Completed Date: 2010-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4137-47 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Separation Chemotaxis, Leukocyte / immunology* Choristoma / immunology, metabolism Flow Cytometry Interleukin-17 / biosynthesis, immunology* Lung Diseases / immunology, virology Lymph Nodes* Mice Mice, Inbred C57BL Mice, Knockout Mucus / metabolism Receptors, CCR7 / deficiency, genetics, immunology Respiratory Syncytial Virus Infections / immunology*, pathology* Respiratory Syncytial Viruses Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI036302/AI/NIAID NIH HHS; AI073876/AI/NIAID NIH HHS; R01 AI036302-14/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ccr7 protein, mouse; 0/Interleukin-17; 0/Receptors, CCR7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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