PMID- 22738676
OWN - NLM
STAT- MEDLINE
DCOM- 20130131
LR  - 20220330
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 130
IP  - 5
DP  - 2012 Nov
TI  - IL-33 induces innate lymphoid cell-mediated airway inflammation by activating 
      mammalian target of rapamycin.
PG  - 1159-1166.e6
LID - S0091-6749(12)00856-1 [pii]
LID - 10.1016/j.jaci.2012.05.018 [doi]
AB  - 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 p110delta 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.
CI  - Copyright (c) 2012 American Academy of Allergy, Asthma & Immunology. Published by 
      Mosby, Inc. All rights reserved.
FAU - Salmond, Robert J
AU  - Salmond RJ
AD  - Division of Immunology, Infection and Inflammation, University of Glasgow, 
      Glasgow, United Kingdom.
FAU - Mirchandani, Ananda S
AU  - Mirchandani AS
FAU - Besnard, Anne-Gaelle
AU  - Besnard AG
FAU - Bain, Calum C
AU  - Bain CC
FAU - Thomson, Neil C
AU  - Thomson NC
FAU - Liew, Foo Y
AU  - Liew FY
LA  - eng
GR  - G0801198/MRC_/Medical Research Council/United Kingdom
GR  - G0902003/MRC_/Medical Research Council/United Kingdom
GR  - G9818261/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120626
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Il1rl1 protein, mouse)
RN  - 0 (Il33 protein, mouse)
RN  - 0 (Interleukin-1 Receptor-Like 1 Protein)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-33)
RN  - 0 (Interleukin-5)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, Interleukin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Class Ia Phosphatidylinositol 3-Kinase/metabolism
MH  - Humans
MH  - Immunity, Cellular/drug effects/genetics
MH  - Immunity, Innate/drug effects/genetics
MH  - Interleukin-1 Receptor-Like 1 Protein
MH  - Interleukin-13/metabolism
MH  - Interleukin-33
MH  - Interleukin-5/metabolism
MH  - Interleukins/*administration & dosage
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Pneumonia/chemically induced/*drug therapy/*immunology
MH  - Receptors, Interleukin/genetics
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Th2 Cells/*drug effects/immunology/transplantation
PMC - PMC3664950
EDAT- 2012/06/29 06:00
MHDA- 2013/02/01 06:00
PMCR- 2012/11/01
CRDT- 2012/06/29 06:00
PHST- 2012/01/10 00:00 [received]
PHST- 2012/05/16 00:00 [revised]
PHST- 2012/05/18 00:00 [accepted]
PHST- 2012/06/29 06:00 [entrez]
PHST- 2012/06/29 06:00 [pubmed]
PHST- 2013/02/01 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - S0091-6749(12)00856-1 [pii]
AID - 10.1016/j.jaci.2012.05.018 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2012 Nov;130(5):1159-1166.e6. doi: 
      10.1016/j.jaci.2012.05.018. Epub 2012 Jun 26.