烟雾暴露变应性鼻炎ILC2细胞与糖皮质激素敏感相关性及其机制研究

Corticosteroids(CS) resistance occurred in some allergic rhinitis(AR) patients, whether this type of CS resistance will be regulated by cigarette smoke remains unclear. Our previous researches indicated that cigarette smoke induced nasal epithelial thickening, eosinophilia and high level of IgE in AR mice with high expression of GATA3 and T-bet. Calpeptin ameliorated cigarette smoke-induced airway inflammation by inhibiting μ-calpain, m-calpain and IκBα in the lungs of mice and BEAS-2B cells. Therefore our speculation is that cigarette smoke may promote the occurrence and development of CS resistant AR through aggravating abnormal CS receptor sensitivity and anti-inflammatory mechanism. Our team will conduct the following studies: the effect of cigarette smoke on AR rats and their CS receptor sensitivity and anti-inflammatory mechanisms; the impact of cigarette smoking on AR patients and their ILC2s, Th2 cells, CS receptor sensitivity and anti-inflammatory mechanisms; the effect of dexamethasone and calpeptin administrated respectively on cigarette smoke-induced AR rats and their CS receptor sensitivity and anti-inflammatory mechanisms. Our research would clarify the effects and mechanisms about cigarette smoke aggravating CS resistant AR and provide new ideas and strategies for its further treatment.

变应性鼻炎（AR）患者存在糖皮质激素（CS）治疗抵抗现象，香烟烟雾暴露是否改变AR激素抵抗尚不清楚。我们前期研究表明烟雾暴露AR小鼠鼻黏膜上皮增厚、嗜酸性粒细胞浸润和外周血IgE水平升高更明显，GATA3、T-bet表达升高。calpeptin抑制香烟烟雾引起的小鼠肺及BEAS-2B细胞μ-calpain、m-calpain和IκBα的表达，减轻下呼吸道炎症。据此我们设想：香烟烟雾暴露引起CS受体、抗炎机制异常，促进CS抵抗型AR的发生发展。本课题拟研究：香烟烟雾暴露对AR大鼠、CS受体、抗炎机制的影响及经地塞米松干预后的变化。烟雾暴露对AR患者ILC2细胞、Th2细胞、相关细胞因子的影响及CS受体、抗炎机制的变化。calpeptin对烟雾暴露AR大鼠、CS受体及抗炎机制的影响。本研究将明确烟雾暴露加重CS抵抗型AR的作用及机制，为烟雾暴露的CS抵抗型AR的治疗提供新的思路与策略。

变应性鼻炎（AR）患者存在糖皮质激素（CS）治疗抵抗现象，香烟烟雾暴露是否改变AR激素抵抗尚不清楚。我们前期研究表明烟雾暴露AR小鼠鼻黏膜上皮增厚、嗜酸性粒细胞浸润和外周血IgE水平升高更明显，GATA3、T-bet表达升高。calpeptin抑制香烟烟雾引起的小鼠肺及BEAS-2B细胞μ-calpain、m-calpain和IκBα的表达，减轻下呼吸道炎症。据此我们设想：香烟烟雾暴露引起CS受体、抗炎机制异常，促进CS抵抗型AR的发生发展。在本课题中，我们证实香烟烟雾暴露可以加重AR中的Th2炎症反应，导致糖皮质激素抵抗。其机制可能与DNA甲基转移酶3a(DNMT3A)表达降低、干扰素调节因子1(IRF1)表达增加有关。此外，我们还发现calpeptin可以抑制IRF1的表达，从而治疗香烟烟雾暴露大鼠的AR相关糖皮质激素抵抗。这些数据表明，calpeptin可能下调IRF1，从而治疗与香烟烟雾暴露相关的AR中的糖皮质激素抵抗。