活性氧（ROS）是肠黏膜固有免疫重要组分，但过量ROS是诱发肠黏膜免疫炎症损伤的关键环节，在炎症性肠病（IBD）发病中起重要作用。DUOX2是肠道ROS关键酶还原性辅酶II家族新成员，在IBD患者肠黏膜表达明显增加，但具体机制不明。我们前期发现DUOX2有诱导自噬的作用，抑制DUOX2后可改善结肠炎小鼠的症状及组织学炎症；而异常激活的自噬已被证实可促进内源性炎症介质HMGB1的释放从而介导肠道黏膜免疫炎症，我们已证实HMGB1在IBD患者肠黏膜表达明显增加。基于此，我们推测DUOX2介导的氧化应激可能通过调控自噬通路进而促进HMGB1的释放，在IBD发病中发挥重要作用。本研究拟采用荧光定量PCR、蛋白印迹、免疫组化、RNA干扰等技术，使用患者来源的微小肠及基因敲除动物模型，首次阐明DUOX2通过调控自噬促进HMGB1释放介导肠黏膜炎症发生发展的潜在机制，有望为IBD的治疗提供新靶点。

Reactive oxygen species (ROS) are essential components of intestinal mucosal innate immunity. Excessive generation of ROS can cause inflammation, which in turn leads to mucosal damage. Therefore, ROS is suggested to play an important role in the etiology and pathogenesis of inflammatory bowel disease (IBD). Dual oxidase 2 (DUOX2), a new member of NADPH oxidase, which is mainly expressed along the gastrointestinal tract, is highly upregulated in patients with IBD. However, the regulatory mechanism of DUOX2 in IBD is still underdetermined. Our preliminary data showed that DUOX2 derived ROS induced autophagy and aggravated mice colitis. Whereas, deficiency of DUOX2 alleviated the symptoms and intestinal mucosal inflammation of mice colitis. In addition, abnormally activated autophagy has been identified to promote the release of intrinsic inflammatory mediator high mobility group box-1 protein (HMGB1). And we also found that the expression of HMGB1 was significantly elevated in IBD patients. Therefore, we propose a hypothesis that DUOX2 plays an important role in pathogenesis of IBD by regulating autophagy-induced HMGB1 release. In the current study, we will test the regulatory mechanism of DUOX2 in autophagy and HMGB1 by applying multiple techniques including qRT-PCR, immunoblot, immunostaining and RNA interference on IBD patient-derived organoids culture systems and DUOX2 knockout mice systems. The discovery of DUOX2 as novel regulator in the pathogenesis of IBD by promoting autophagy -induced HMGB1 makes it a new candidate mediator of physiopathological processes and potential therapeutic target for IBD patients.