期刊
AUTOPHAGY
卷 12, 期 10, 页码 1876-1885出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1207857
关键词
autophagy; eye; inflammasome; innate immunity; macrophage; uveitis
类别
资金
- NIH [R01EY019287, DK097845]
- NIH Vision Core Grant [P30EY02687]
- Carl Marshall Reeves and Mildred Almen Reeves Foundation Inc. Award
- Research to Prevent Blindness Inc. Career Development Award
- Jeffrey Fort Innovation Fund (RSA), NIH [U19AI109725, R01AI084887]
- Grants-in-Aid for Scientific Research [26713005, 15K14951, 15H01380] Funding Source: KAKEN
Autophagy is critical for maintaining cellular homeostasis. Organs such as the eye and brain are immunologically privileged. Here, we demonstrate that autophagy is essential for maintaining ocular immune privilege. Deletion of multiple autophagy genes in macrophages leads to an inflammation-mediated eye disease called uveitis that can cause blindness. Loss of autophagy activates inflammasome-mediated IL1B secretion that increases disease severity. Inhibition of caspase activity by gene deletion or pharmacological means completely reverses the disease phenotype. Of interest, experimental uveitis was also increased in a model of Crohn disease, a systemic autoimmune disease in which patients often develop uveitis, offering a potential mechanistic link between macrophage autophagy and systemic disease. These findings directly implicate the homeostatic process of autophagy in blinding eye disease and identify novel pathways for therapeutic intervention in uveitis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据