Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration
So Gun Hong1, Noriko Sato2, Fanny Legrand3
1Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute.
Blood
|July 14, 2020
Summary
Glucocorticoids rapidly decrease blood eosinophils by directing them to the bone marrow via the CXCR4 receptor. This finding explains the mechanism behind glucocorticoid-induced eosinopenia in eosinophilic disorders.
Area of Science:
- Immunology
- Pharmacology
Background:
- Glucocorticoids are primary treatments for eosinophilic disorders, causing a rapid drop in circulating eosinophils.
- The mechanism behind this glucocorticoid-induced eosinopenia has remained unclear for decades.
Purpose of the Study:
- To elucidate the mechanism of glucocorticoid-induced eosinopenia.
- To investigate the role of CXCR4 in this process.
Main Methods:
- Compared glucocorticoid response in circulating eosinophils across three species (mice, rhesus macaques, humans).
- Utilized positron emission tomography/computed tomography imaging to track labeled eosinophils in rhesus macaques before and after glucocorticoid administration.
- Examined the effect of selective CXCR4 blockade on eosinophil reduction.
Main Results:
- Rhesus macaque response to glucocorticoids mirrored human response.
- Glucocorticoids induced rapid eosinophil migration to the bone marrow.
- CXCR4 blockade significantly reduced or abolished the early decrease in blood eosinophils.
Conclusions:
- Glucocorticoid-induced eosinopenia is mediated by CXCR4-dependent eosinophil migration to the bone marrow.
- Findings offer insights into glucocorticoid action in eosinophilic disorders, with implications for glucocorticoid resistance and novel therapies.
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