Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease.

Autor: McAlpine CS; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Park J; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Griciuc A; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Kim E; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Choi SH; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Iwamoto Y; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kiss MG; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Christie KA; Center for Genomic Medicine, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Vinegoni C; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Poller WC; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mindur JE; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Chan CT; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., He S; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Janssen H; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Wong LP; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Downey J; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Singh S; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Anzai A; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kahles F; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Jorfi M; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Feruglio PF; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Sadreyev RI; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Weissleder R; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kleinstiver BP; Center for Genomic Medicine, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Nahrendorf M; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Tanzi RE; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. rtanzi@mgh.harvard.edu., Swirski FK; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. filip.swirski@mssm.edu.; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. filip.swirski@mssm.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Jul; Vol. 595 (7869), pp. 701-706. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1038/s41586-021-03734-6
Abstrakt: Communication within the glial cell ecosystem is essential for neuronal and brain health 1-3 . The influence of glial cells on the accumulation and clearance of β-amyloid (Aβ) and neurofibrillary tau in the brains of individuals with Alzheimer's disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions 4,5 . Here we show, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of AD. Upon recognition of Aβ deposits, microglia increase their expression of IL-3Rα-the specific receptor for IL-3 (also known as CD123)-making them responsive to IL-3. Astrocytes constitutively produce IL-3, which elicits transcriptional, morphological, and functional programming of microglia to endow them with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Aβ and tau. These changes restrict AD pathology and cognitive decline. Our findings identify IL-3 as a key mediator of astrocyte-microglia cross-talk and a node for therapeutic intervention in AD.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: