Journal article
Impaired autophagy in macrophages promotes inflammatory eye disease
Autophagy, Vol.12(10), pp.1876-1885
10/02/2016
DOI: 10.1080/15548627.2016.1207857
PMCID: PMC5066937
PMID: 27463423
Abstract
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.
Details
- Title: Subtitle
- Impaired autophagy in macrophages promotes inflammatory eye disease
- Creators
- Andrea Santeford - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineLuke A Wiley - Steven W. Dezii Translational Vision Research Facility, Stephen A. Wynn Institute for Vision Research Department of Ophthalmology & Visual Sciences, Carver College of Medicine, University of IowaSunmin Park - Department of Pathology and Immunology, Washington University School of MedicineSonya Bamba - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineRei Nakamura - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineAbdelaziz Gdoura - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineThomas A Ferguson - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineP. Kumar Rao - Department of Ophthalmology and Visual Sciences, Washington University School of MedicineJun-Lin Guan - Department of Cancer Biology, University of Cincinnati College of MedicineTatsuya Saitoh - Institute for Enzyme Research, Tokushima UniversityShizuo Akira - Laboratory of Host Defense, WPI Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka UniversityRamnik Xavier - Center for Computational and Integrative Biology and Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical SchoolHerbert W Virgin - Department of Molecular Microbiology, Washington University School of MedicineRajendra S Apte - Department of Medicine, Washington University School of Medicine
- Resource Type
- Journal article
- Publication Details
- Autophagy, Vol.12(10), pp.1876-1885
- Publisher
- Taylor & Francis
- DOI
- 10.1080/15548627.2016.1207857
- PMID
- 27463423
- PMCID
- PMC5066937
- ISSN
- 1554-8627
- eISSN
- 1554-8635
- Grant note
- name: HHS | National Institutes of Health (NIH), award: R01EY019287; name: HHS | National Institutes of Health (NIH), award: U19AI109725; name: HHS | National Institutes of Health (NIH), award: R01AI084887; DOI: 10.13039/100010657, name: Carl Marshall Reeves and Mildred Alman Reeves Foundation Inc.; name: HHS | National Institutes of Health (NIH), award: DK097845; name: Research to Prevent Blindness (RPB); name: HHS | National Institutes of Health (NIH), award: P30EY02687
- Language
- English
- Date published
- 10/02/2016
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983979980102771
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