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Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease.
McAlpine, Cameron S; Park, Joseph; Griciuc, Ana; Kim, Eunhee; Choi, Se Hoon; Iwamoto, Yoshiko; Kiss, Máté G; Christie, Kathleen A; Vinegoni, Claudio; Poller, Wolfram C; Mindur, John E; Chan, Christopher T; He, Shun; Janssen, Henrike; Wong, Lai Ping; Downey, Jeffrey; Singh, Sumnima; Anzai, Atsushi; Kahles, Florian; Jorfi, Mehdi; Feruglio, Paolo Fumene; Sadreyev, Ruslan I; Weissleder, Ralph; Kleinstiver, Benjamin P; Nahrendorf, Matthias; Tanzi, Rudolph E; Swirski, Filip K.
Affiliation
  • McAlpine CS; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Park J; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Griciuc A; Friedman Brain Institute and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 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; 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.
  • Kiss MG; 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.
  • Christie KA; Center for Systems Biology and Department of Radiology, 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 Genomic Medicine, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 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; Cardiovascular Research Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Janssen H; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Wong LP; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and 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; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
  • Kahles F; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Jorfi M; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Feruglio PF; Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Sadreyev RI; Center for Systems Biology and Department of Radiology, 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; 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.
  • Nahrendorf M; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Tanzi RE; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
  • Swirski FK; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nature ; 595(7869): 701-706, 2021 07.
Article in En | MEDLINE | ID: mdl-34262178
ABSTRACT
Communication within the glial cell ecosystem is essential for neuronal and brain health1-3. The influence of glial cells on the accumulation and clearance of ß-amyloid (Aß) and neurofibrillary tau in the brains of individuals with Alzheimer's disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions4,5. 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 Aß 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 Aß 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Astrocytes / Interleukin-3 / Microglia / Alzheimer Disease Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Nature Year: 2021 Document type: Article Affiliation country: United States Publication country: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Astrocytes / Interleukin-3 / Microglia / Alzheimer Disease Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Nature Year: 2021 Document type: Article Affiliation country: United States Publication country: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM