@article{Patel:2019:10.1126/sciimmunol.aax7006,
author = {Patel, DF and Peiro, T and Bruno, N and Vuononvirta, J and Akthar, S and Puttur, F and Pyle, CJ and Suveizdyte, K and Walker, SA and Singanayagam, A and Carlin, LM and Gregory, LG and Lloyd, CM and Snelgrove, R},
doi = {10.1126/sciimmunol.aax7006},
journal = {Science Immunology},
pages = {1--18},
title = {Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation},
url = {http://dx.doi.org/10.1126/sciimmunol.aax7006},
volume = {4},
year = {2019}
}

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TY  - JOUR
AB  - Neutrophil mobilization, recruitmentand clearancemust be tightly regulated asover-exuberant neutrophilic inflammation isimplicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophilstherapeutically have failed to consider theirpleiotropic functions and theimplications of disrupting fundamental regulatory pathways that govern their turnover duringhomeostasisand  inflammation.Using  thehouse  dust  mite(HDM)model  of  allergic airways disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated TH2  inflammation,  epithelial  remodelling  and  airway  resistance. Mechanistically,  this  was attributable  to  astriking  increase  insystemic G-CSF concentrations, which are  ordinarily negatively regulated in the periphery by transmigrated lung neutrophils. Intriguingly, we found that increasedG-CSF augmented allergic sensitization in HDM  exposed  animals bydirectly acting  on airway ILC2s  toelicitcytokine production.Moreover,  increased  systemic  G-CSF promoted  expansion  of  bone  marrow monocyte progenitor  populations,  which  resulted  in enhanced  antigen  presentation  by  an augmented  peripheral  monocyte-derived  dendritic  cell pool.By modelling the effects of neutrophil depletion, our studies have therefore uncovered previously   unappreciated   roles   for   G-CSF   in   modulating   ILC2   function   and   antigen presentation.  More  broadly,they  highlight  an  unexpected  regulatory  role  for  neutrophils  in limiting TH2 allergic airway inflammation.
AU  - Patel,DF
AU  - Peiro,T
AU  - Bruno,N
AU  - Vuononvirta,J
AU  - Akthar,S
AU  - Puttur,F
AU  - Pyle,CJ
AU  - Suveizdyte,K
AU  - Walker,SA
AU  - Singanayagam,A
AU  - Carlin,LM
AU  - Gregory,LG
AU  - Lloyd,CM
AU  - Snelgrove,R
DO  - 10.1126/sciimmunol.aax7006
EP  - 18
PY  - 2019///
SN  - 2470-9468
SP  - 1
TI  - Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation
T2  - Science Immunology
UR  - http://dx.doi.org/10.1126/sciimmunol.aax7006
UR  - http://hdl.handle.net/10044/1/74249
VL  - 4
ER  - 

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