Volume 10 Supplement 2

Canadian Society of Allergy and Clinical Immunology and AllerGen Abstracts 2014

Open Access

IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34+ progenitor cells

  • Pia Reece1Email author,
  • Gail M Gauvreau1,
  • Roma Sehmi2 and
  • Judah A Denburg1
Allergy, Asthma & Clinical Immunology201410(Suppl 2):A60

https://doi.org/10.1186/1710-1492-10-S2-A60

Published: 18 December 2014

Background

Intrauterine environmental exposures have been shown to influence neonatal immunity and subsequent allergic disease development [1]. We have previously shown that cord blood (CB) progenitor cells of high atopic risk infants have reduced toll-like receptor (TLR) expression and produce fewer lipopolysaccharide (LPS)-stimulated eosinophil-basophil (Eo/B) colonies, compared to low-atopic risk infants. In the present study, we investigated whether a surrogate ex vivo TH2 milieu (i.e., either IL-4 or IL-13), could represent an underlying mechanism to explain our previous findings.

Methods

CB CD34+ cells from healthy donors were cultured with IL-4 or IL-13 (in combination with LPS) and assessed for TLR-2, TLR-4, and TLR-9 expression using flow cytometry, as well as Eo/B differentiation using methylcellulose cultures. Pharmacological inhibitors were added to the methylcellulose cultures to determine the effect of blocking IL-4 or IL-13 signalling in CB CD34+ cells in relation to Eo/B colony forming unit (CFU) formation.

Results

Stimulation of CD34+ cells with IL-4 or IL-13 trended to decreased expression of TLR-2 (p=0.063), whereas IL-4, but not IL-13, reduced Eo/B CFU formation in the presence of LPS. The latter was found to be dependent on IL-4Rα and not IL-13Rα1.

Conclusions

Thus, the responsiveness of CB CD34+ progenitor cells to LPS is differentially regulated by the TH2 cytokines, IL-4 and IL-13, and may be related to TLR expression on these cells. Therefore, in utero interactions between placental-derived pro-allergic cytokines and neonatal progenitor cells influences CD34+ phenotype and function, with implications for Eo/B-mediated inflammatory responses in early life.

Authors’ Affiliations

(1)
Division of Clinical Immunology and Allergy, McMaster University
(2)
Asthma Research Group, Firestone Institute for Respiratory Health, McMaster University Hamilton

References

  1. Hinz D, Bauer M, Roder S, Olek S, Huehn J, Sack U, Borte M, Simon JC, Lehmann I, Herberth G, for the LINA study group: Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year. Allergy. 2012, 67: 380-389. 10.1111/j.1398-9995.2011.02767.x.View ArticlePubMedGoogle Scholar

Copyright

© Reece et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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