2.50
Hdl Handle:
http://hdl.handle.net/10033/621191
Title:
Suppression of Th17-polarized airway inflammation by rapamycin.
Authors:
Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie
Abstract:
Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.
Affiliation:
TWINCORE, Zentrum für experimentelle und kliische Infektionsforschung GmbH, Deodor-Lynen-Sr. 7, 30625 Hannover, Germany.
Citation:
Suppression of Th17-polarized airway inflammation by rapamycin. 2017, 7 (1):15336 Sci Rep
Journal:
Scientific reports
Issue Date:
10-Nov-2017
URI:
http://hdl.handle.net/10033/621191
DOI:
10.1038/s41598-017-15750-6
PubMed ID:
29127369
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorJoean, Oanaen
dc.contributor.authorHueber, Anjaen
dc.contributor.authorFeller, Felixen
dc.contributor.authorJirmo, Adan Charien
dc.contributor.authorLochner, Matthiasen
dc.contributor.authorDittrich, Anna-Mariaen
dc.contributor.authorAlbrecht, Melanieen
dc.date.accessioned2017-12-01T13:08:06Z-
dc.date.available2017-12-01T13:08:06Z-
dc.date.issued2017-11-10-
dc.identifier.citationSuppression of Th17-polarized airway inflammation by rapamycin. 2017, 7 (1):15336 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid29127369-
dc.identifier.doi10.1038/s41598-017-15750-6-
dc.identifier.urihttp://hdl.handle.net/10033/621191-
dc.description.abstractBecause Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleSuppression of Th17-polarized airway inflammation by rapamycin.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und kliische Infektionsforschung GmbH, Deodor-Lynen-Sr. 7, 30625 Hannover, Germany.en
dc.identifier.journalScientific reportsen

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