GM-CSF intrinsically controls eosinophil accumulation in the setting of allergic airway inflammation

The Journal of Allergy and Clinical Immunology
Samuel Philip NobsM Kopf

Abstract

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...Continue Reading

Citations

Oct 16, 2019·The Journal of Experimental Medicine·John A Hamilton
Nov 21, 2019·The European Respiratory Journal·Young-Min KimSeung-Woo Lee
Aug 2, 2020·Immunology and Cell Biology·Olivier LamiableFranca Ronchese
Feb 17, 2019·International Journal of Molecular Sciences·Francesco BorrielloGianni Marone
Oct 23, 2019·Signal Transduction and Targeted Therapy·Seyyed Shamsadin Athari
Jun 25, 2020·Nature Reviews. Immunology·Frederick M LangJohn A Hamilton
Jan 14, 2021·The Journal of Allergy and Clinical Immunology·Samuel Philip NobsManfred Kopf
Oct 18, 2020·Signal Transduction and Targeted Therapy·Seyyed Shamsadin Athari
Mar 27, 2021·Frontiers in Pharmacology·Daniele Pala, Marco Pistis
Sep 3, 2019·The Journal of Allergy and Clinical Immunology·Leonard B BacharierHirohito Kita
Nov 2, 2020·European Journal of Pharmacology·Miroslava MolitorisovaSona Franova
Nov 28, 2021·Nutrients·Roos E M VerstegenLinette E M Willemsen

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