Human Hemopoietic Progenitor Cell Toll-like and Thymic Stromal Lymphopoietin Receptor Expression and Function in Allergic Asthmatic Subjects

Rationale: We demonstrated that cord blood human progenitor cells (HPC) from high allergic risk newborns expressed Toll-like receptors (TLR) less abundantly than low allergic risk infants. We also have recently found a key role for thymic stromal lymphopoietin (TSLP) in human eosinophil and basophil differentiation from HPC in allergic subjects. However, TLR or TLR-induced TSLP receptor (TSLPR) expression by HPC has never been studied in allergic asthmatic subjects.

Methods: The study group comprised 10 healthy and 11 allergic asthmatic subjects.  Asthmatics underwent diluent-controlled bronchial allergen challenge. Peripheral blood (PB) was collected from both healthy and asthmatic subjects (before and 24 hours after diluent/allergen challenge). The PB HPC-enriched cell population was stimulated ex vivo with TLR-2 (lipoteichoic acid, LTA), TLR-4 (lipopolysaccharide, LPS) or TLR-9 (ODN2006) ligands. HPC TLR and TSLPR expression after TLR ligation were examined pre- and post-bronchial allergen challenge by flow cytometry.

Results: Asthmatic HPC expressed significantly less TLR-2 and TLR-9, compared to non-asthmatic HPC (p<0.05), with a similar trend for TLR-4 (p=0.057). TLR-4 stimulation of asthmatic HPC yielded significantly higher expression of TSLPR, compared with HPC from healthy controls (22.51±4.24% vs 11.6±1.34%, respectively; p<0.05), with a similar trend for asthmatic HPC after TLR-9 stimulation (p=0.054). Allergen challenge led to a further increase in TSLPR expression by LPS-stimulated HPC, compared to diluent (32.37±4.14% vs 18.25±4.94%, respectively; p<0.05).

Conclusions: These findings support the involvement of HPC in the initiation and persistence of airways inflammation during infection-driven asthma exacerbations.