IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34 + progenitor cells
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ALLERGY, ASTHMA & CLINICAL IMMUNOLOGY
MEETING ABSTRACT
Open Access
IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34+ progenitor cells Pia Reece1*, Gail M Gauvreau1, Roma Sehmi2, Judah A Denburg1 From Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2014 Ottawa, ON, Canada. 23-26 October 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 lowatopic 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.
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’ details 1 Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario Canada, L8S 4K1. 2Asthma Research Group, Firestone Institute for Respiratory Health, McMaster University Hamilton, Ontario, Canada L8N 4A6. Published: 18 December 2014 Reference 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. doi:10.1186/1710-1492-10-S2-A60 Cite this article as: Reece et al.: IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34+ progenitor cells. Allergy, Asthma and Clinical Immunology 2014 10(Suppl 2):A60.
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-4Ra and not IL-13Ra1.
* Correspondence: [email protected] 1 Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario Canada, L8S 4K1 Full list of author inf
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