Combinatorial IL-17RB, ST2, and TSLPR Signaling in Dendritic Cells of Patients with Allergic Rhinitis

Objectives Myeloid dendritic cells (DCs) in patients with allergic rhinitis (AR) express higher levels of IL-17RB, ST2, and TSLPR. However, their functional roles in DCs are much less clear. This study aimed to determine the combined effects of these three receptor signals on the T cell-polarizing function of DCs in AR patients. Methods Monocyte-derived DCs (mo-DCs) were generated and stimulated with Toll-like receptor (TLR) 1-9 ligands. Der.p1-induced mo-DCs were stimulated with different combinations of IL-25, IL-33, and TSLP to determine phenotypic characteristics and then co-cultured with CD4(+) T cells to assess Th2 cytokine production. Expression levels of IL-17RB, ST2, and TSLPR on myeloid DCs (mDCs) from peripheral blood of AR and healthy subjects were detected to confirm the association of these receptors with disease severity. Results TLR ligands induced AR-derived mo-DCs to increase IL-17RB, ST2, and TSLPR expression by varying degrees; among these, Der.p1 was the strongest inducer. Der.p1-induced mo-DCs from AR showed increased OX40L expression. IL-25, IL-33, and TSLP (alone or in double combination) significantly increased OX40L expression on Der.p1-induced mo-DCs from AR, thereby increasing the production of IL-4, IL-5, and IL-13 in co-cultured CD4(+) T cells; triple combination further enhanced these effects. The percentage of IL-17RB(+)ST2(+)TSLPR(+) mDCs was increased in AR, higher in moderate to severe phase than in mild phase, and positively correlated with the percentages of IL-4(+), IL-5(+), and IL-13(+) T cells. Conclusion A combination of IL-17RB, ST2, and TSLPR signals amplified the Th2-polarizing function of DCs and was associated with disease severity in AR patients.