Effects of Blocking NLRP3 Inflammasome on Type II Innate Lymphoid Cell Response in Allergic Rhinitis.

Abstract

Background: Type 2 innate lymphoid cells (ILC2s) and NLRP3 inflammasome are related to allergic and inflammatory responses. NLRP3 inflammasome inhibitor MCC950 was demonstrated to ameliorate allergic rhinitis (AR) in animal models.

Objective: To elucidate the effect of MCC950 on ILC2 responses in AR.

Methods: NLRP3 inflammasome, ILC2s, IL-5+ILC2s, IL-13+ILC2s, and Th2-related factors were examined in 30 AR patients. ILC2s were identified as Lin-CRTH2+CD127+lymphocytes. ILC2s isolated from PBMCs were stimulated with LPS plus ATP. The effect of MCC950, IL-1β, and IL-18 on ILC2 responses was detected by flow cytometry. AR models were established in 60 BALB/c mice. Nasal symptoms and ILC2 responses in the AR models after MCC950 treatment were detected. Human nasal epithelial cells were stimulated with IL-13 (10 ng/mL) and treated with MCC950 (10 μM).

Results: AR patients showed activated NLRP3 inflammasome and increased ILC2 responses compared to controls. NLRP3 inflammasome levels in the AR patients were positively related to the proportion of ILC2s, IL-5+ILC2s, and IL-13+ILC2s in total PBMCs. MCC950 treatment or IL-1β/IL-18 suppression inhibited ILC2 proliferation and Th2-related factors (GATA3, RORα, IL-5, and IL-13). MCC950 administration alleviated frequencies of nasal rubbing and sneezes in the AR models. ILC2s, IL-5+ILC2s, and IL-13+ILC2s in mice were reduced by MCC950. MCC950 inhibited NLRP3 inflammasome in the in vitro models of AR.

Conclusion: MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.