Department of Otolaryngology, General Hospital of Central Theater Command, Wuhan, Hubei, China.
Iran J Immunol. 2023 Sep 1;20(3):287-302. doi: 10.22034/iji.2023.96966.2473.
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.
To elucidate the effect of MCC950 on ILC2 responses in AR.
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).
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.
MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.
2 型固有淋巴细胞（ILC2）和 NLRP3 炎性小体与过敏和炎症反应有关。NLRP3 炎性小体抑制剂 MCC950 已被证明可改善动物模型中的过敏性鼻炎（AR）。
阐明 MCC950 对 AR 中 ILC2 反应的影响。
在 30 例 AR 患者中检查 NLRP3 炎性小体、ILC2、IL-5+ILC2、IL-13+ILC2 和 Th2 相关因子。ILC2 被鉴定为 Lin-CRTH2+CD127+淋巴细胞。从 PBMC 中分离出 ILC2 并用 LPS 加 ATP 刺激。通过流式细胞术检测 MCC950、IL-1β 和 IL-18 对 ILC2 反应的影响。在 60 只 BALB/c 小鼠中建立 AR 模型。检测 MCC950 治疗后 AR 模型中的鼻部症状和 ILC2 反应。用 IL-13（10ng/mL）刺激人鼻上皮细胞并用 MCC950（10μM）处理。
与对照组相比，AR 患者表现出激活的 NLRP3 炎性小体和增加的 ILC2 反应。AR 患者的 NLRP3 炎性小体水平与总 PBMC 中 ILC2、IL-5+ILC2 和 IL-13+ILC2 的比例呈正相关。MCC950 治疗或抑制 IL-1β/IL-18 抑制了 ILC2 的增殖和 Th2 相关因子（GATA3、RORα、IL-5 和 IL-13）。MCC950 给药减轻了 AR 模型中鼻擦和打喷嚏的频率。MCC950 降低了小鼠中的 ILC2、IL-5+ILC2 和 IL-13+ILC2。MCC950 抑制了 AR 体外模型中的 NLRP3 炎性小体。
MCC950 抑制了 AR 和小鼠模型中的 ILC2 反应，表明阻断 NLRP3 炎性小体可能是 AR 临床治疗的一个有前途的靶点。
