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Through their interactions with components of the blood\u2013brain barrier (BBB), astrocytes not only regulate BBB function, they also sense molecules produced by peripheral immune cells, including cytokines. Here, we review the interactions between immune cells and astrocytes and their roles in health and neurological diseases, with a special focus on multiple sclerosis (MS). We highlight known pathways that participate in astrocyte crosstalk with microglia, NK cells, T cells, and other cell types; their contribution to the pathogenesis of neurological diseases; and their potential value as therapeutic targets.<\/jats:p>","DOI":"10.1084\/jem.20202715","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T13:26:24Z","timestamp":1626960384000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["Functional immune cell\u2013astrocyte interactions"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-8826","authenticated-orcid":true,"given":"Liliana M.","family":"Sanmarco","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurological Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-0161","authenticated-orcid":true,"given":"Carolina M.","family":"Polonio","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurological Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 1"},{"name":"Neuroimmune Interactions Laboratory, Immunology Department, Instituto de Ci\u00eancias Biom\u00e9dicas IV, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0689-6384","authenticated-orcid":true,"given":"Michael A.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurological Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 1"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-0736","authenticated-orcid":true,"given":"Francisco J.","family":"Quintana","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurological Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 1"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"2023072803193612300_bib1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cell.2018.05.002","article-title":"Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement","volume":"174","author":"Adamsky","year":"2018","journal-title":"Cell."},{"key":"2023072803193612300_bib2","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.neuron.2017.09.056","article-title":"Cell biology of astrocyte-synapse interactions","volume":"96","author":"Allen","year":"2017","journal-title":"Neuron."},{"key":"2023072803193612300_bib3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1126\/science.aat0473","article-title":"Glia as architects of central nervous system formation and function","volume":"362","author":"Allen","year":"2018","journal-title":"Science."},{"key":"2023072803193612300_bib4","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1126\/science.1206936","article-title":"The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence","volume":"334","author":"Alvarez","year":"2011","journal-title":"Science."},{"key":"2023072803193612300_bib5","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1038\/s41590-020-0776-4","article-title":"Meningeal \u03b3\u03b4 T cells regulate anxiety-like behavior via IL-17a signaling in neurons","volume":"21","author":"Alves de Lima","year":"2020","journal-title":"Nat. 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