Search

There were gender differences in the prevalence and severity of allergic diseases. Group 2 innate lymphoid cells (ILC2s) were recently reported to play a critical role in allergic diseases. We investigated the sex-dependent differences in ILC2-dominant allergic airway inflammation model using T\B cell-deficient mice, and determined the gender differences of ILC2 levels in patients with asthma and allergic rhinitis. Female mice exhibited higher levels of inflammatory infiltration and large production of IL-5 and IL-13, especially for ILC2 levels compared to male mice with the induction of IL-33. However, no significant differences were found for the levels of circulating ILC2s between the genders of patients. The treatment of testosterone significantly decreased the intracellular type 2 cytokines in ILC2s and the proliferation of pure ILC2s in response to epithelial cytokines. Our study suggested the sex differences and the involvement of androgen on ILC2s in allergic diseases.

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 sought to address the roles of mDCs and pDCs in regulating ILC2 function in AR. Methods mDCs and pDCs were cocultured 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 with 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 signal transducer and activator of transcription 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.