The Effect of IL-18 on Group 2 Innate Lymphoid Cells in Allergic Rhinitis

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation by producing interleukin-4 (IL-4), IL-5, IL-9, and IL-13. IL-18 can promote T helper 2 cell (Th2) response by inducing IL-4, and IL-13 production from mast cells and basophils. However, the regulation of IL-18 on ILC2s remained unknown. OBJECTIVE: To investigate the regulatory role of IL-18 in inducing the type 2 innate lymphoid cells. METHODS: Twenty patients with allergic rhinitis (AR) and 20 controls were enrolled. The mRNA and protein levels of IL-18 in serum, as well as the frequencies of ILC2 in peripheral blood mononuclear cells (PBMCs) were measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. The ILC2s were sorted and the mRNA expression of IL-18 receptor in ILC2 was analyzed by real-time PCR. The effects of IL-18 on the proliferation and type 2 cytokine production were detected by tritiated thymidine incorporation test, real-time PCR, and ELISA, respectively. RESULTS: The levels of IL-18 mRNA and protein were significantly higher in AR patients than in the controls (P<0.05). The frequency of ILC2 in peripheral blood was elevated in the AR patients than in the controls. After stimulation by IL-18 and house dust mite (HDM), the expression of IL-18 receptor (IL-18R) by ILC2 was significantly up-regulated. The tritiated thymidine incorporation results showed that IL-18 promoted the proliferation of ILC2 in a dose-dependent manner. IL-18 also induced the expression of IL-5 and IL-13 proteins by ILC2. CONCLUSION: Our results confirmed -for the first time- the effect of IL-18 in innate immunity, which was demonstrated by direct effect on the differentiation and function of ILC2.

Interleukin-33 Promotes Th2/Th17 Response in Eosinophilic and Non-Eosinophilic Nasal Polyps.

BACKGROUND: Interleukin-33 (IL-33) is reported to be involved in Th2-skewed eosinophilic inflammation. A recent study also found that IL-33 exerted opposite effects on Th17 response in different diseases. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (NPs) was not explored. OBJECTIVES: The purpose of this study was to investigate the expression and function of IL-33 in chronic rhinosinusitis with NPs. MATERIALS AND METHODS: NP tissues from 60 NP patients and normal tissues of the inferior turbinate from 20 controls were sampled in operation. Immunochemistry was performed to identify eosinophilic or non-eosinophilic NPs. The expressions of IL-33 and Th1/2/17 cytokines were compared between different subtypes of NPs. The effect of IL-33 on Th response was detected in dispersed nasal polyp cells (DNPCs), and the signaling pathways involved in the process were detected using Western blot. RESULTS: The concentration of IL-33 was significantly elevated in both eosinophilic and non-eosinophilic NPs compared with controls. By in vitro study, we found that IL-33 can induce IL-4 and IL-5 production from eosinophilic DNPCs through the PI3K/AKT pathway, whereas IL-33 can induce IL-17 production from non-eosinophilic DNPCs through the ERK1/2 pathway. CONCLUSION: IL-33 is involved in Th2/Th17 response in NPs. Our study suggests that different types of NPs need a different treatment target.

Sublingual Immunotherapy Decreases Expression of Interleukin-33 in Children with Allergic Rhinitis.

OBJECTIVES: To identify the expression of IL-33 during SLIT (Sublingual immunotherapy) in AR (Allergic rhinitis) children. METHODS: Thirty children received house dust mite (HDM) allergen extract for SLIT and thirty children received placebo in this study. Serum and nasal lavage samples of cases and controls were collected at different time points during SLIT. Interleukin (IL)-33 and other cytokines were estimated in these samples by enzyme-linked immuno sorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were prepared and stimulated with rhIL-33 (with or without other stimulators) at different time points during SLIT. RESULTS: The present results showed that both serum and nasal lavage of IL-33 levels decreased significantly after 12 mo treatment and this trend maintained at least until 24 mo. The decreased nasal IL-33 level was positively correlated to local Th2 cytokines and increased IL-10 expression at 2 y post SLIT treatment. In vitro experiments showed that IL-33 promotes IL-4 and IL-5 and inhibits IL-10 expression by peripheral blood mononuclear cells (PBMCs) in AR. CONCLUSIONS: Decreased IL-33 expression during SLIT may contribute to low Th2 response and enhanced Regulatory T cell cytokines expression. Thus, IL-33 maybe an important predictor during SLIT.