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While we and others have shown that T cell cytokines differentially regulate leukocyte entry into perivascular spaces and regional parenchymal localization in murine models of MS, the molecular mechanisms of this latter process are poorly understood. Here, we demonstrate that astrocytes exhibit region\u2010specific responses to T cell cytokines that promote hindbrain versus spinal cord neuroinflammation. Analysis of cytokine receptor expression in human astrocytes showed region\u2010specific responsiveness to Th1 and Th17 inflammatory cytokines. Consistent with this, human and murine astrocytes treated with these cytokines exhibit differential expression of the T cell localizing molecules VCAM\u20101 and CXCR7 that is both cytokine and CNS region\u2010specific. Using in vivo models of spinal cord versus brain stem trafficking of myelin\u2010specific T cells and astrocyte\u2010specific deletion strategies, we confirmed that Th1 and Th17 cytokines differentially regulate astrocyte expression of VCAM\u20101 and CXCR7 in these locations. Finally, stereotaxic injection of individual cytokines into the hindbrain or spinal cord revealed region\u2010 and cytokine\u2010specific modulation of localizing cue expression by astrocytes. These findings identify a role for inflammatory cytokines in mediating local astrocyte\u2010dependent mechanisms of immune cell trafficking within the CNS during neuroinflammation.<\/jats:p>","DOI":"10.1002\/glia.23783","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T08:43:24Z","timestamp":1579596204000},"page":"1361-1374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Astrocyte\u2010T cell crosstalk regulates region\u2010specific neuroinflammation"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-9580","authenticated-orcid":false,"given":"Jessica L.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute Cleveland Clinic Foundation  Cleveland Ohio"},{"name":"Department of Medicine Washington University School of Medicine  St. Louis 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