GM-CSF intrinsically controls eosinophil accumulation in the setting of allergic airway inflammation.
Eosinophils
GM-CSF
allergic airway inflammation
asthma
chemokinesis
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
10
07
2017
revised:
09
08
2018
accepted:
24
08
2018
pubmed:
24
9
2018
medline:
24
4
2020
entrez:
24
9
2018
Statut:
ppublish
Résumé
Eosinophils are a therapeutic target in asthmatic patients, and GM-CSF has been suggested to control various aspects of eosinophil biology, including development, function, and survival. However, to date, the role of GM-CSF signaling in eosinophils in vivo is largely unclear. We sought to elucidate the role of GM-CSF signaling in asthmatic inflammation. Wild-type and GM-CSF receptor α (Csf2ra)-deficient mice reconstituted with Csf2ra-proficient alveolar macrophages were subjected to different models of airway inflammation to evaluate the effect of GM-CSF signaling deficiency on asthmatic inflammation in general and on eosinophils in particular. We demonstrate that GM-CSF signaling, although being largely dispensable for eosinophil development at steady state, intrinsically promotes accumulation of eosinophils in the lung during allergic airway inflammation. In contrast, chitin-induced eosinophil accumulation in the peritoneal cavity occurs independent of GM-CSF, indicating organ specificity. We show that GM-CSF induces chemokinesis and promotes eosinophil survival in vitro, which likely contribute to eosinophil accumulation in the airways in vivo. GM-CSF intrinsically promotes eosinophil accumulation in the setting of pulmonary allergic inflammation.
Sections du résumé
BACKGROUND
Eosinophils are a therapeutic target in asthmatic patients, and GM-CSF has been suggested to control various aspects of eosinophil biology, including development, function, and survival. However, to date, the role of GM-CSF signaling in eosinophils in vivo is largely unclear.
OBJECTIVE
We sought to elucidate the role of GM-CSF signaling in asthmatic inflammation.
METHODS
Wild-type and GM-CSF receptor α (Csf2ra)-deficient mice reconstituted with Csf2ra-proficient alveolar macrophages were subjected to different models of airway inflammation to evaluate the effect of GM-CSF signaling deficiency on asthmatic inflammation in general and on eosinophils in particular.
RESULTS
We demonstrate that GM-CSF signaling, although being largely dispensable for eosinophil development at steady state, intrinsically promotes accumulation of eosinophils in the lung during allergic airway inflammation. In contrast, chitin-induced eosinophil accumulation in the peritoneal cavity occurs independent of GM-CSF, indicating organ specificity. We show that GM-CSF induces chemokinesis and promotes eosinophil survival in vitro, which likely contribute to eosinophil accumulation in the airways in vivo.
CONCLUSION
GM-CSF intrinsically promotes eosinophil accumulation in the setting of pulmonary allergic inflammation.
Identifiants
pubmed: 30244025
pii: S0091-6749(18)31329-0
doi: 10.1016/j.jaci.2018.08.044
pii:
doi:
Substances chimiques
Csf2ra protein, mouse
0
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1513-1524.e2Informations de copyright
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.