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Article: B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance

TitleB7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance
Authors
Issue Date2005
Citation
Journal of Immunology, 2005, v. 174, n. 5, p. 3000-3005 How to Cite?
AbstractThe recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7KP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechalleage of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In audition, expression of two major Th2-associated costimulatory molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eostaophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.
Persistent Identifierhttp://hdl.handle.net/10722/292531
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 1.558
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGajewska, Beata U.-
dc.contributor.authorTafuri, Anna-
dc.contributor.authorŚwirski, Filip K.-
dc.contributor.authorWalker, Tina-
dc.contributor.authorJohnson, Jill R.-
dc.contributor.authorShea, Theresa-
dc.contributor.authorShahinian, Arda-
dc.contributor.authorGoncharova, Susanna-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorStämpfli, Martin R.-
dc.contributor.authorJordana, Manel-
dc.date.accessioned2020-11-17T14:56:40Z-
dc.date.available2020-11-17T14:56:40Z-
dc.date.issued2005-
dc.identifier.citationJournal of Immunology, 2005, v. 174, n. 5, p. 3000-3005-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/292531-
dc.description.abstractThe recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7KP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechalleage of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In audition, expression of two major Th2-associated costimulatory molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eostaophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.-
dc.languageeng-
dc.relation.ispartofJournal of Immunology-
dc.titleB7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4049/jimmunol.174.5.3000-
dc.identifier.pmid15728513-
dc.identifier.scopuseid_2-s2.0-20044387031-
dc.identifier.volume174-
dc.identifier.issue5-
dc.identifier.spage3000-
dc.identifier.epage3005-
dc.identifier.isiWOS:000227172100069-
dc.identifier.issnl0022-1767-

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