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Interleukin\u20101 (IL\u20101) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL\u20101 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL\u20101\u03b1 is an important ligand contributing to the CNS dependence on IL\u20101 and that IL\u20101 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue\u2010specific requirements for IL\u20101 in driving innate immunity and suggest that IL\u20101\u2010mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury\u2010 and disease\u2010associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders.<\/jats:p>","DOI":"10.1002\/eji.201444748","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T10:08:42Z","timestamp":1415095722000},"page":"525-530","source":"Crossref","is-referenced-by-count":29,"title":["Requirement for interleukin\u20101 to drive brain inflammation reveals tissue\u2010specific mechanisms of innate immunity"],"prefix":"10.1002","volume":"45","author":[{"given":"James A.","family":"Giles","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Greenhalgh","sequence":"additional","affiliation":[{"name":"Centre for Research in Neuroscience Montreal General Hospital McGill University Health Center  Montreal Quebec"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Davies","sequence":"additional","affiliation":[{"name":"The Roslin Institute &amp; R(D)SVS University of Edinburgh  Easter Bush Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Denes","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tovah","family":"Shaw","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Coutts","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Rothwell","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry W.","family":"McColl","sequence":"additional","affiliation":[{"name":"The Roslin Institute &amp; R(D)SVS University of Edinburgh  Easter Bush Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Allan","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01040.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5376-06.2007"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1109766"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05528.2001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.101"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00684.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.054882"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200409"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4049\/jimmunol.157.1.291","article-title":"Effect of endotoxin in IL\u20101 beta\u2010deficient mice","volume":"157","author":"Fantuzzi G.","year":"1996","journal-title":"J. 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