Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Front Immunol. 2024 Feb 19;15:1364839. doi: 10.3389/fimmu.2024.1364839. eCollection 2024.
Intrapancreatic activation of trypsinogen caused by alcohol or high-fat intake and the subsequent autodigestion of the pancreas tissues by trypsin are indispensable events in the development of acute pancreatitis. In addition to this trypsin-centered paradigm, recent studies provide evidence that innate immune responses triggered by translocation of intestinal bacteria to the pancreas due to intestinal barrier dysfunction underlie the immunopathogenesis of acute pancreatitis. Although severe acute pancreatitis is often associated with pancreatic colonization by fungi, the molecular mechanisms linking fungus-induced immune responses to the development of severe acute pancreatitis are poorly understood. Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein that mediates innate immune responses to fungi and bacteria. Mutations in is a risk factor for Parkinson's disease and Crohn's disease, both of which are driven by innate immune responses to gut organisms.
In this Minireview article, we discuss how activation of LRRK2 by the recognition of fungi induces severe acute pancreatitis.
酒精或高脂肪摄入引起的胰蛋白酶原在胰内激活，随后胰蛋白酶自身消化胰腺组织，这是急性胰腺炎发展过程中不可或缺的事件。除了这种以胰蛋白酶为中心的模式外，最近的研究还提供了证据，表明由于肠道屏障功能障碍导致肠道细菌易位到胰腺，从而引发固有免疫反应，这是急性胰腺炎发病机制中的基础。尽管重症急性胰腺炎常与胰腺真菌感染有关，但将真菌诱导的免疫反应与重症急性胰腺炎的发展联系起来的分子机制仍知之甚少。富含亮氨酸重复激酶 2（LRRK2）是一种多功能蛋白，可介导对真菌和细菌的固有免疫反应。LRRK2 突变是帕金森病和克罗恩病的一个风险因素，这两种疾病都是由对肠道生物体的固有免疫反应驱动的。
在这篇小综述文章中，我们讨论了真菌识别引发的 LRRK2 激活如何导致重症急性胰腺炎。
