2016
DOI: 10.1080/15548627.2016.1207857
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Impaired autophagy in macrophages promotes inflammatory eye disease

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 pharmacologi… Show more

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Cited by 62 publications
(59 citation statements)
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“…Thus, mice lacking Atg5 (but not Ulk1 ) in the RPE display defective 11- cis -retinal generation and reduced vision, which can be transiently corrected by the administration of all- trans -retinol 268 . Mice with a macrophage-specific deletion of Atg5 as well as mice carrying the Atg16l1 T300A mutation exhibit increased susceptibility to lipopolysaccharide-induced uveitis that is associated with increased inflammasome activation 269 . In humans, the ATG16L1 T300A mutation is associated with Crohn’s disease (see above), which is also linked to an increased predisposition for uveitis 270 .…”
Section: Autophagy As a Therapeutic Targetmentioning
confidence: 99%
“…Thus, mice lacking Atg5 (but not Ulk1 ) in the RPE display defective 11- cis -retinal generation and reduced vision, which can be transiently corrected by the administration of all- trans -retinol 268 . Mice with a macrophage-specific deletion of Atg5 as well as mice carrying the Atg16l1 T300A mutation exhibit increased susceptibility to lipopolysaccharide-induced uveitis that is associated with increased inflammasome activation 269 . In humans, the ATG16L1 T300A mutation is associated with Crohn’s disease (see above), which is also linked to an increased predisposition for uveitis 270 .…”
Section: Autophagy As a Therapeutic Targetmentioning
confidence: 99%
“…Autophagy‐deficient macrophages display enhanced activation of the NLRP3‐inflammasome after exposure to silica particles and excess release of IL‐18. Autophagy deficiency in macrophages also worsens inflammasome‐mediated eye disease …”
Section: Inflammatory Diseases and Autophagy Deficiencymentioning
confidence: 99%
“…Another or additional mechanism could be autophagy, as recent work on myeloid cells indicates that impaired autophagy mediates increased inflammation. A conditional knock-out of Atg5 or Atg7 in macrophages correlated with increased severity of uveitis (Santeford et al, 2016), liver fibrosis (Lodder et al, 2015), or colitis (Lee et al, 2016). Loss of the autophagy protein ATG16L1 is associated with Crohn's disease and resulted in enhanced pro-inflammatory cytokine production of macrophages in response to stress (Saitoh et al, 2008;Murthy et al, 2014).…”
Section: Introductionmentioning
confidence: 99%