类甲壳素酶蛋白SI-CLP在变应性鼻炎发病中的作用及机制

Dust mite is the most widespread aeroallergen. Chitin is the major element of dust mite. Chitinases are evolutionarily conserved hydrolases that could degrade chitin which are expressed in mammals. SI-CLP is the novel chitinase-like proteins, which lacks the enzymatic activity but retain the ability to bind chitin with high affinity. It implies that they may function in the recognition of pathogen-associated molecular patterns encoded in chitin, thereby signaling to the host immune system to mount an appropriate pathogen-directed attack. SI-CLP is widely expressed in mammals including human and rodent. SI-CLP is expressed by epithelium, specialized tissue macrophages and sinusoidal endothelial cells..SI-CLP protein was detected in the cellular fraction of BAL from patients with chronic bronchitis, however, expression levels varied. The highest SI-CLP expression was detected in patient with sarcoidosis, undergoing corticoid therapy. Expression of SI-CLP in macrophages was strongly up-regulated by the Th2 cytokine IL-4 and by dexamethasone, while the administration of dexamethasone could depress the secretion of SI-CLP. All of these clues indicate the SI-CLP may play an important role in airway disease. The function of SI-CLP in allergic rhinitis is poorly understood. No published study reveals the role of SI-CLP in allergic disease.

吸入性过敏原中最常见的过敏原为尘螨，尘螨的体表含有大量甲壳素。甲壳素酶能够降解甲壳素，在进化过程中被保留，在哺乳动物体内有表达。SI-CLP是最新发现的一种类甲壳素酶蛋白，广泛表达于哺乳动物包括人类和啮齿类动物，不具有甲壳素酶活性但它保留了可以与甲壳素相结合的位点，这预示了该蛋白可能通过病原相关的分子识别模式来将信号传导至免疫系统，导致机体的免疫反应。SI-CLP表达于多种器官的上皮细胞, 窦腔内皮细胞和巨噬细胞。以往研究提示它的表达在慢性肺部疾病患者的肺泡盥洗液细胞沉淀中均有表达，在使用激素治疗的患者中升高得更明显，使用地塞米松联合IL-4刺激体外分化的巨噬细胞可以促进其生成，但地塞米松的使用会抑制它的分泌，提示SI-CLP可能与呼吸道疾病相关，而且它是唯一与糖皮质激素使用相关的类甲壳素酶蛋白。然而它在AR发病中的作用至今尚未有相关研究。

变应性鼻炎（Allergic Rhinitis, AR）是指特应性个体接触吸入性变应原后发生在鼻腔黏膜的非感染性炎症，是由IgE介导的I型超敏反应。AR在我国的发病率也逐年上升，已由2005年的11.1%增长至2011年的17.6%。但目前对AR的发病机制并不是十分清楚，另外AR指南推荐的一线治疗方法包括药物治疗和变应原脱敏治疗（Allergen Immunotherapy AIT），其中变应原脱敏治疗不仅能缓解症状， AR患者停止治疗后长期获益，还能起到预防作用，预防新的过敏性疾病产生及对新的过敏原产生过敏，但接受脱敏治疗后仍有一部分的患者预后不佳，脱敏治疗效果评价的客观指标缺失，在治疗前或治疗早期就可以反应预后的指标缺失。负责人近年来在国家自然科学基金青项目支持下，围绕国人AR发病机制及脱敏治疗机制进行研究，取得了原创性结果：1. 明确B细胞亚群和T-B细胞相互作用在AR发病机制及AIT治疗机制中的作用，结果“CD23 expression on switched memory B cells bridges T-B cell interaction in allergic rhinitis”发表在Allergy 2020 (IF=13.146)；2. 明确AR患者外周血II型辅助性T（Th2）和II型滤泡辅助性T（Tfh2）细胞的趋化特点，文章已被《中华耳鼻咽喉头颈外科杂志》接收；3. 发现CC10蛋白-SI-CLP蛋白-Th2细胞活化轴在AR中的作用：文章正在撰写。