Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors
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2021Access:
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Scott, L.M. and Vincent, E.E. and Hudson, N. and Neal, C. and Jones, N. and Lavelle, E.C. and Campbell, M. and Halestrap, A.P. and Dick, A.D. and Theodoropoulou, S., Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors, JCI Insight, 6, 8, 2021Abstract:
It remains unresolved how retinal pigment epithelial cell metabolism is regulated following immune activation to maintain
retinal homeostasis and retinal function. We exposed retinal pigment epithelium (RPE) to several stress signals,
particularly Toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic
glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-
33) as a key metabolic checkpoint that antagonizes the Warburg effect to ensure the functional stability of the RPE. The
identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its
extracellular “alarmin” activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative
pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declined and resultant
bioenergetic switching was aligned with altered mitochondrial morphology. Our data not only shed new light on the
molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors but also uncover a
potentially novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator.
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http://people.tcd.ie/lavelleehttp://people.tcd.ie/campbem2
http://people.tcd.ie/hudsonna
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JCI Insight6
8
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retinal pigment, epithelial cell metabolism, metabolic checkpoint regulator, Glucose metabolism, Metabolism, Mitochondria, Ophthalmology, RetinopathyDOI:
http://dx.doi.org/10.1172/jci.insight.129429Metadata
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