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Here, we report that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus of aged brains. ILC2 in the aged brain are long-lived, are relatively resistant to cellular senescence and exhaustion, and are capable of switching between cell cycle dormancy and proliferation. They are functionally quiescent at homeostasis but can be activated by IL-33 to produce large amounts of type 2 cytokines and other effector molecules in vitro and in vivo. Intracerebroventricular transfer of activated ILC2 revitalized the aged brain and enhanced the cognitive function of aged mice. Administration of IL-5, a major ILC2 product, was sufficient to repress aging-associated neuroinflammation and alleviate aging-associated cognitive decline. Targeting ILC2 in the aged brain may provide new avenues to combat aging-associated neurodegenerative disorders.<\/jats:p>","DOI":"10.1084\/jem.20190915","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T10:56:50Z","timestamp":1576839410000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":97,"title":["Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline"],"prefix":"10.1084","volume":"217","author":[{"given":"Ivan Ting Hin","family":"Fung","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima","family":"Sankar","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-9183","authenticated-orcid":true,"given":"Lisa S.","family":"Robison","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Neural Stem Cell Institute, Rensselaer, NY 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-4511","authenticated-orcid":true,"given":"Shanti S.","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail E.","family":"Salinero","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Neural Stem Cell Institute, Rensselaer, NY 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albany Medical College, Albany, NY 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy L.","family":"Kuentzel","sequence":"additional","affiliation":[{"name":"Center for Functional Genomics, University at Albany\u2013State University of New York, Rensselaer, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8061-5846","authenticated-orcid":true,"given":"Sridar V.","family":"Chittur","sequence":"additional","affiliation":[{"name":"Center for Functional Genomics, University at Albany\u2013State University of New York, Rensselaer, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Temple","sequence":"additional","affiliation":[{"name":"Neural Stem Cell Institute, Rensselaer, NY 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-7362","authenticated-orcid":true,"given":"Kristen L.","family":"Zuloaga","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-0986","authenticated-orcid":true,"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 1"},{"name":"Department of Medicine, Albany Medical College, Albany, NY 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"2026041423510340400_bib1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nprot.2014.005","article-title":"Intravascular staining for discrimination of vascular and tissue leukocytes","volume":"9","author":"Anderson","year":"2014","journal-title":"Nat. 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