IL-17RB+DC亚群促进变应性鼻炎Th2炎症的作用和机制研究

研究表明功能特异性树突状细胞（DC）亚群精细调控了变应性鼻炎(AR)的鼻黏膜Th2炎症；IL-25在变应性疾病中具有重要促Th2炎症作用，但机制仍不清。我们最近报道了AR患者外周血中IL-17RB+DC亚群显著增多，LPS可诱导该DC亚群的表达，而IL-25可增强其Th2极化功能，据此我们提出科学假设：IL-17RB+DC亚群是AR中调控Th2炎症的特异性DC亚群，其受TLR信号刺激诱导而产生，进而受IL-25调控而促进下游的Th2炎症反应。本研究拟通过人体外实验和AR动物模型，采用DC体外培养、干预和动物体内过继转移的实验策略，深入研究IL-17RB+DC亚群在AR中的促Th2炎症作用和胞内信号转导机制，明晰诱导产生IL-17RB+DC亚群的信号，并探讨该亚群对糖皮质激素的敏感性。本研究将有助于阐明该DC亚群在AR发病中的作用和机制，为靶向该DC亚群的精准治疗提供实验和理论依据。

Studies have shown that functional subsets of dendritic cells (DC) fine-tune the nasal mucosal Th2 inflammation of allergic rhinitis (AR); IL-25 has an important role in Th2 inflammation in allergic diseases, but the mechanism is still not clear. We recently reported a significant increase in IL-17RB+ DC subpopulation in peripheral blood of patients with AR, and LPS can induce the expression of this subset of DCs, and IL-25 can enhance its Th2-polarizing function. Therefore, we hypothesize that IL-17RB+ DC subset is a specific DC subpopulation that regulates Th2 inflammation in AR, which is induced by stimulation of TLR signaling, and regulated by IL-25 to promote the downstream Th2 inflammation. The purpose of this study is to investigate the role of IL-17RB+ DC subset in promoting Th2 inflammation and the corresponding intracellular signal transduction in AR, elucidate the signals that induced the generation of IL-17RB+DC subset, and explore the sensitivity of this DC subset to glucocorticoid, by using a combination of in vivo animal and in vitro human studies. This study will be helpful to elucidate the role and mechanism of IL-17RB+ DC subset in the pathogenesis of AR, and provide experimental and theoretical basis for DC-subset-targeting precision treatment.