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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...

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Autores principales: Salmond, Robert J., Mirchandani, Ananda S., Besnard, Anne-Gaelle, Bain, Calum C., Thomson, Neil C., Liew, Foo Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mosby 2012
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.
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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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