Document Details

Document Type : Article In Journal 
Document Title :
IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin
IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin
 
Document Language : English 
Abstract : 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. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. 
ISSN : 0091-6749 
Journal Name : Journal of Allergy and Clinical Immunology 
Volume : 130 
Issue Number : 5 
Publishing Year : 1433 AH
2012 AD 
Article Type : Article 
Added Date : Wednesday, March 9, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Robert J SalmondSalmond, Robert J Investigator  
Ananda S MirchandaniMirchandani, Ananda S Researcher  
Anne-Gaelle BesnardBesnard, Anne-Gaelle Researcher  
Calum C BainBain, Calum C Researcher  
Neil C ThomsonThomson, Neil C Researcher  
Foo Y LiewLiew, Foo Y Researcher  

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