Effects of myeloid and plasmacytoid dendritic cells on ILC2s in patients with allergic rhinitis

Abstract Background Group 2 innate lymphoid cells (ILC2s) were reported to serve a critical role in allergic diseases. Myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) play significant roles in allergic immune response. However, effects of DCs on ILC2s in allergic diseases, especially for patients with allergic rhinitis (AR), remain unclear. Objective We aimed to address the roles of mDCs and pDCs in regulating ILC2 function in AR. Methods mDCs and pDCs were co-cultured with human PBMCs isolated from patients with AR or ILC2s to measure soluble or intracellular Th2 cytokines, transcription factors, signaling pathways in ILC2s, and the following mechanisms were further investigated. The levels of peripheral IL-33+mDCs, pDCs and ILC2s were studied in patients under an inhaled allergen challenge. Results We confirmed the presence of ILC2s, mDCs and pDCs in the nasal mucosa of patients of AR. Both allogenic and autologous mDCs were found to activate ILC2s from patients with AR to produce Th2 cytokines, and increase the levels of GATA-3 and STAT signaling pathways, in which IL-33-producing mDCs exerted the major role by binding on ST2 on ILC2s. We further identified high levels of IL-33+mDCs and ILC2s in patients with AR under antigen challenge. Activated pDCs inhibited the cytokine production of ILC2s isolated from patients with AR by secretion of IL-6. Conclusions mDCs promote ILC2 function by the IL-33/ST2 pathway, and activation of pDCs suppresses ILC2 function through IL-6 in patients with AR. Our findings provide new understanding of the interplay between DCs and ILC2s in allergic diseases.