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IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34+ progenitor cells
Allergy, Asthma & Clinical Immunology volume 10, Article number: A60 (2014)
Intrauterine environmental exposures have been shown to influence neonatal immunity and subsequent allergic disease development . 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.
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.
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.
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.
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.
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Reece, P., Gauvreau, G.M., Sehmi, R. et al. IL-4 and IL-13 regulate TLR expression and eosinophil-basophil differentiation of cord blood CD34+ progenitor cells. All Asth Clin Immun 10, A60 (2014). https://doi.org/10.1186/1710-1492-10-S2-A60
- Progenitor Cell
- Cord Blood
- Colony Form Unit
- Healthy Donor
- Environmental Exposure