H2S具有抗炎、抗氧化应激、抗凋亡等多种机制参与高血压发病；H2S生成酶CBS敲除抑制Treg细胞的分化。我们前期工作发现，高血压患者外周血淋巴细胞内源性CSE/H2S下调，药物控制血压后恢复。据此我们提出假说-内源性CSE/H2S系统可调节CD4 T细胞亚群分化参与高血压发病。本项目拟从1）探讨高血压发病时淋巴细胞内源性CSE/H2S及Treg/Th17亚群的改变及相关性；2）探讨干预内源性CSE/H2S系统对CD4+ T细胞不同亚型分化的影响；3）探讨CSE/H2S通过硫氢化LKB1，进而激活AMPK，促使Treg分化而抑制Th 17分化的分子机制；4）应用CD4细胞选择性敲除CSE小鼠，在血管紧张素刺激下血压的改变及CD4亚群的改变，并回输野生型CD4进行校正，探讨该通路是否参与高血压发病。本项目从免疫调节机制阐明了气体信号分子H2S参与高血压保护的新机制。

Hydrogen sulfide (H2S) is an anti-inflammation, anti-oxidative stress, anti-apoptosis gasotransmitter participating in pathogenesis of hypertension. The key enzyme of H2S-CBS deficiency inhibited Treg differentiation. Our previous work found that endogenous CSE/H2S system but not CBS of peripheral blood lymphocyte in untreated hypertension patients down-regulated comparison to health individual; which recovered while blood pressure controlled by drugs. According to these findings, we make a hypothesis: endogenous CSE/H2S mediates CD4 T cell subtype differentiation by sulfhydration LKB1 in the pathogenesis of hypertension. The present proposal plans to: 1) to investigate the changes of endogenous CSE/H2S in lymphocytes and Treg/Th17 numbers, and the correlation between CSE/H2S and Treg/Th17 ratio during hypertension development; 2) to investigate the role of CSE/H2S in CD4+ T cell subtype differentiation; 3) to investigate the pathway of sulfhydration LKB1 by CSE/H2S, to activation AMPK to mediate CD4 T cell subtype differentiation; 4) to confirm the phenotype of CSE specific knockout in CD4 T cell in hypertension development, and observe the changes of CD4 T cell subtypes and rescue effect while transfusion wild-type CD4 T cell. The present proposal highlight a novel molecular mechanism of H2S protection in pathogenesis of hypertension.