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IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin
BACKGROUND: The IL-1 family cytokine IL-33 is involved in the induction of airway inflammation in allergic patients and after viral infection. Several cell types, including CD4(+) T(H)2 cells and the recently described type 2 innate lymphoid cells (ILCs), are targets for IL-33, yet the mechanisms by...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mosby
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664950/ https://www.ncbi.nlm.nih.gov/pubmed/22738676 http://dx.doi.org/10.1016/j.jaci.2012.05.018 |
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author | Salmond, Robert J. Mirchandani, Ananda S. Besnard, Anne-Gaelle Bain, Calum C. Thomson, Neil C. Liew, Foo Y. |
author_facet | Salmond, Robert J. Mirchandani, Ananda S. Besnard, Anne-Gaelle Bain, Calum C. Thomson, Neil C. Liew, Foo Y. |
author_sort | Salmond, Robert J. |
collection | PubMed |
description | BACKGROUND: The IL-1 family cytokine IL-33 is involved in the induction of airway inflammation in allergic patients and after viral infection. Several cell types, including CD4(+) T(H)2 cells and the recently described type 2 innate lymphoid cells (ILCs), are targets for IL-33, yet the mechanisms by which this cytokine modulates their activation are not clear. OBJECTIVES: Our goal was to investigate a role for mammalian target of rapamycin (mTOR) signaling in the activation of T(H)2 and ILC responses and the induction of airway inflammation by IL-33. METHODS: We biochemically determined the effect of IL-33 on mTOR activation in T(H)2 cells and ILCs and examined the effect of this signaling pathway in vivo using a murine model of IL-33–induced lung inflammation. RESULTS: We found that IL-33 induces mTOR activation through p110δ phosphoinositide 3-kinase and that blockade of the mTOR pathway inhibited IL-33–induced IL-5 and IL-13 production by T(H)2 cells and ILCs. Furthermore, use of a ribosomal protein S6 kinase 1 inhibitor implicated a role for ribosomal protein S6 kinase 1 in IL-33–induced mTOR-dependent cytokine production. Intranasal administration of IL-33 to wild-type mice induced airway inflammation, whereas adoptive transfer of wild-type ILCs to IL-33 receptor–deficient (St2(−/−)) mice recapitulated this response. Importantly, coadministration of the mTOR inhibitor rapamycin reduced IL-33–dependent ILC, macrophage, and eosinophil accumulation; cytokine secretion; and mucus deposition in the airways. CONCLUSION: These data reveal a hitherto unrecognized role of mTOR signaling in IL-33–driven, ILC-dependent inflammation in vivo and suggest that manipulation of this pathway might represent a target for therapeutic intervention for airway inflammation. |
format | Online Article Text |
id | pubmed-3664950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Mosby |
record_format | MEDLINE/PubMed |
spelling | pubmed-36649502013-05-28 IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin Salmond, Robert J. Mirchandani, Ananda S. Besnard, Anne-Gaelle Bain, Calum C. Thomson, Neil C. Liew, Foo Y. J Allergy Clin Immunol Mechanisms of Allergy and Clinical Immunology BACKGROUND: The IL-1 family cytokine IL-33 is involved in the induction of airway inflammation in allergic patients and after viral infection. Several cell types, including CD4(+) T(H)2 cells and the recently described type 2 innate lymphoid cells (ILCs), are targets for IL-33, yet the mechanisms by which this cytokine modulates their activation are not clear. OBJECTIVES: Our goal was to investigate a role for mammalian target of rapamycin (mTOR) signaling in the activation of T(H)2 and ILC responses and the induction of airway inflammation by IL-33. METHODS: We biochemically determined the effect of IL-33 on mTOR activation in T(H)2 cells and ILCs and examined the effect of this signaling pathway in vivo using a murine model of IL-33–induced lung inflammation. RESULTS: We found that IL-33 induces mTOR activation through p110δ phosphoinositide 3-kinase and that blockade of the mTOR pathway inhibited IL-33–induced IL-5 and IL-13 production by T(H)2 cells and ILCs. Furthermore, use of a ribosomal protein S6 kinase 1 inhibitor implicated a role for ribosomal protein S6 kinase 1 in IL-33–induced mTOR-dependent cytokine production. Intranasal administration of IL-33 to wild-type mice induced airway inflammation, whereas adoptive transfer of wild-type ILCs to IL-33 receptor–deficient (St2(−/−)) mice recapitulated this response. Importantly, coadministration of the mTOR inhibitor rapamycin reduced IL-33–dependent ILC, macrophage, and eosinophil accumulation; cytokine secretion; and mucus deposition in the airways. CONCLUSION: These data reveal a hitherto unrecognized role of mTOR signaling in IL-33–driven, ILC-dependent inflammation in vivo and suggest that manipulation of this pathway might represent a target for therapeutic intervention for airway inflammation. Mosby 2012-11 /pmc/articles/PMC3664950/ /pubmed/22738676 http://dx.doi.org/10.1016/j.jaci.2012.05.018 Text en © 2012 Mosby, Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Mechanisms of Allergy and Clinical Immunology Salmond, Robert J. Mirchandani, Ananda S. Besnard, Anne-Gaelle Bain, Calum C. Thomson, Neil C. Liew, Foo Y. IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title_full | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title_fullStr | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title_full_unstemmed | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title_short | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
title_sort | il-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
topic | Mechanisms of Allergy and Clinical Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664950/ https://www.ncbi.nlm.nih.gov/pubmed/22738676 http://dx.doi.org/10.1016/j.jaci.2012.05.018 |
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