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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Retinoic acids up-regulate functional eosinophil-driving receptor CCR3.

S Ueki1, J Nishikawa, Y Yamauchi

  • 1Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan. ueki-shige@nifty.com

Allergy
|June 8, 2013
PubMed
Summary
This summary is machine-generated.

Retinoic acids (RAs) significantly increase functional CCR3 expression on human eosinophils, independent of common cytokines. This vitamin A derivative pathway is crucial for eosinophil accumulation in tissues.

Keywords:
CCR3eosinophilsretinoic acidsvitamin A

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Eotaxins and their receptor CCR3 are critical for eosinophil tissue infiltration in both normal and disease states.
  • The physiological triggers for up-regulating CCR3 on blood-derived human eosinophils remain largely unidentified.

Purpose of the Study:

  • To investigate the role of retinoic acids (RAs) in modulating the expression and function of CCR3 on human eosinophils.
  • To determine if RAs can induce CCR3 expression and enhance eosinophil responsiveness to eotaxins.

Main Methods:

  • Human peripheral blood eosinophils were stimulated with various retinoic acid isomers (9-cis RA, all-trans RA).
  • CCR3 surface expression was quantified using flow cytometry.
  • Functional assays included calcium mobilization and chemotaxis in response to eotaxin-1 (CCL11), with pharmacological modulation of retinoic acid receptor-α (RARα).

Main Results:

  • Both 9-cis RA and all-trans RA significantly induced surface CCR3 expression on eosinophils, irrespective of IL-3 or IL-5 presence.
  • Activation of retinoic acid receptor-α (RARα) was identified as essential for this CCR3 up-regulation.
  • RA-induced CCR3 expression correlated with enhanced eosinophil functional responses, including calcium influx and chemotaxis towards eotaxin-1.

Conclusions:

  • Vitamin A derivatives, specifically retinoic acids, play a significant role in regulating CCR3 expression and function on human eosinophils.
  • This RA-mediated pathway represents a novel mechanism contributing to eosinophil recruitment and tissue accumulation.
  • Targeting retinoic acid signaling could offer new therapeutic strategies for eosinophil-driven inflammatory diseases.