Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
Autophagy. 2022 Jun;18(6):1475-1477. doi: 10.1080/15548627.2022.2040314. Epub 2022 Feb 23.
NLRP3 (NLR family pyrin domain containing 3) inflammasome is a potent mediator of inflammation due to its ability to produce the pro-inflammatory cytokines IL1B (interleukin 1 beta) and IL18 in response to numerous danger signals and pathogens. Mitophagy, a selective form of autophagy, restricts NLRP3 inflammasome activation by limiting the mitochondrial-derived danger signals. Here, we demonstrated that the adaptor protein APPL1 together with its interaction partner RAB5 in early endosomes negatively regulate NLRP3 inflammasome activation via induction of mitophagy in macrophages. Hematopoietic-deletion of exacerbates systemic NLRP3 inflammasome activation in rodent models under obese or septic conditions. Our study identified a new regulatory network between early endosomes and mitochondria in control of NLRP3 inflammasome activation.
NLRP3（NLR 家族包含pyrin 域的 3）炎性小体是一种有效的炎症介质，因为它能够产生促炎细胞因子 IL1B（白细胞介素 1β）和 IL18，以响应多种危险信号和病原体。自噬，一种选择性的自噬形式，通过限制线粒体来源的危险信号来限制 NLRP3 炎性小体的激活。在这里，我们证明衔接蛋白 APPL1 及其在早期内涵体中的相互作用伙伴 RAB5 通过诱导巨噬细胞中的自噬来负调控 NLRP3 炎性小体的激活。在肥胖或脓毒症条件下，造血细胞缺失会加剧啮齿动物模型中的全身 NLRP3 炎性小体激活。我们的研究确定了早期内涵体和线粒体之间控制 NLRP3 炎性小体激活的新调节网络。
