The T_H2-polarizing function of atopic interleukin 17 receptor B-positive dendritic cells up-regulated by...

Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation.

To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance T_H2 responses.

The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c⁺ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4⁺ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry.

LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86⁺ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86⁺ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4⁺ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4⁺ T cells to produce higher level of IL-4 but lower level of IFN-γ.

Atopic IL-17RB⁺ DCs can be up-regulated by LPS and promote a T_H2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.