自身免疫性肝炎是由机体自身免疫反应引起的慢性肝脏炎症疾病，病因复杂，发病机制尚不明确，缺乏有效的治疗手段。已有研究发现白细胞介素22能促进肝细胞再生，参与肝组织修复并保护肝细胞；我们前期研究证实白介素22能改善自身免疫性肝炎，但由于白细胞介素22受体的广泛存在，静脉给药后白细胞介素22能引起全身性的生物学效应，不利于自身免疫性肝炎的治疗。我们推测通过表达白细胞介素22与载脂蛋白AI融合蛋白，利用载脂蛋白AI与肝细胞上B族I型清道夫受体特异性结合可实现白介素22肝靶向递药，使其在肝脏部位发挥抗炎和免疫调节作用治疗自身免疫性肝炎，避免全身给药的不良反应；同时通过探讨细胞自噬、炎性小体及氧化压力在白介素22融合蛋白治疗自身免疫性肝炎中的作用机理，可为临床上应用白细胞介素22融合蛋白靶向治疗自身免疫性肝炎或者联合自噬干预药物、抗氧化药物及抗炎药物增强自身免疫性肝炎的治疗效果提供新的思路和实验依据。

Autoimmune Hepatitis (AIH) is a chronic progressive inflammatory liver disease triggered by body’s autoimmune response. The etiology and pathogenesis of AIH is complex, and the therapeutic strategy is still limited, thus it’s urgent to develop effective therapeutics for the treatment of AIH. Previous studies have found that interleukin 22 could promote liver cell regeneration and participate in liver tissue repairing. Our research also confirmed that interleukin 22 has therapeutic effect on AIH, but as interleukin 22 receptors are widely existed in most cells of different organs, interleukin 22 could induce systemic biological effects after intravenous administration, and is not suitable for the treatment of AIH. Apolipoprotein A-I could specifically bind to Scavenger receptor class B type I (SR-BI) on liver cells, so our proposed study will develop liver-targeted delivery of interleukin 22 through recombinant interleukin 22 and apolipoprotein A-I fusion protein for AIH therapy. Furthermore, the role and mechanisms of autophagy, inflammasomes, and oxidative stress in liver-targeted therapy of AIH by interleukin 22 fusion protein will also be elucidated in this investigation. This study will shed light on the novel therapy of AIH with liver-targeted interleukin 22 and apolipoprotein A-I fusion protein alone or in combination with autophagy inhibitors, anti-inflammatory agents, or antioxidants for the treatment of AIH in clinic.