硫化氢(H2S)是一新型气体信号分子，在机体中发挥重要调节作用。我们前期研究表明肺内源性H2S主要由胱硫醚-γ-裂解酶(CSE) 产生，其抑制哮喘急性气道炎症，但是否参与气道重构却不为人知。Th17为一新型辅助性T细胞，分泌IL-17A/F等，参与气道重构。我们预实验发现慢性哮喘小鼠肺CSE下降，伴随H2S降低；CSE缺陷促进淋巴细胞分泌IL-17A，而外源性H2S抑制IL-17A产生；另外，反复气道炎症导致重构发生；由此，我们推测"肺内源性H2S可能通过影响Th17的分化进而抑制哮喘气道重构发展"。为证实此假设，本研究拟利用野生型(WT)和CSE敲除(KO)小鼠，建立哮喘气道重构模型，给予外源性H2S以及抗IL-17A阻断，体内外观察内外源性H2S对慢性气道重构的差别及对Th17分化的影响。旨在阐明"内源性CSE/H2S系统"在慢性气道重构中的作用，为哮喘气道重构的干预提供新靶点。

Hydrogen sulfide (H2S), is recognized now as a new gasotransmitter for its important regulatory roles in the body. Our previous studies demonstrate that cystathionine gamma-lyase(CSE) is a major H2S-production enzyme in mouse lung,and endogenous H2S inhibits the development of airway inflammation in a mouse model of acute asthma. However, whether and how the endogenous H2S involves in the airway remodeling in chronic asthma remain unknown. Th17 is a new subset of CD4+ T cell, which play an important role in the airway remodeling of chronic asthma through secreting Th17-associated cytokines like interleukin (IL)-17A and IL-17F. Our preliminary experiments have shown that OVA challenge results in the decreases in the CSE expression and endogenous H2S production in the lung in a mouse model of chronic asthma.In vitro experiments, CSE deficiency promotes the secrection of IL-17A in lymphocytes,while exogenous H2S attenuates the production of this cytokine.In addition, repeated airway inflammation causes the development of airway remodeling. According to these results, we hypothesized that CSE-generated endogenous H2S in the lung may play an important role in the pathogenesis of airway remodeling in allergic asthma by influencing the differentiation of Th17. To confirm the hypothesis, we will establish a mouse model of chronic asthma using wild type (WT) and CSE knock out (CSE-KO) mice. With exogenous H2S application or functional experiments with anti-IL-17A in vivo, we will observe the differences in the parameters of airway remodeling and Th17 polarization in WT and CSE-KO mice in vivo and in vitro experiments. The objective of this study is to clarify the important roles of endogenous CSE/H2S system in the pathogenesis of airway remodeling in asthma and provide a new therapeutic target for chronic asthma.