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U.S.A."],"published-print":{"date-parts":[[2019,10,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The study addresses a basic immunology topic with considerable clinical relevance, namely the nature of the pathogenic T helper cells that drive autoimmune disorders like multiple sclerosis (MS) and inflammatory arthritis. Using mouse MS, we identify precursors of the encephalitogenic\/pathogenic T cells based on their dependence on the protease inhibitor SerpinB1. Newly identified signature genes reveal the unusual nature of these T cells that combine (\n                    <jats:italic>i<\/jats:italic>\n                    ) inflammatory cytokine secretion, (\n                    <jats:italic>ii<\/jats:italic>\n                    ) a cytolytic system, and (\n                    <jats:italic>iii<\/jats:italic>\n                    ) extreme rapid proliferation. We demonstrate that their survival\/expansion depends on SerpinB1 and involves regulation of a proliferation-associated protease-mediated cell suicide mechanism. Importantly, we discovered that cell surface CXCR6 is an exquisite marker of pathogenic T helper cells and demonstrated that anti-CXCR6 treatment has potential to prevent or mitigate MS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1905762116","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T20:35:27Z","timestamp":1569270927000},"page":"20635-20643","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["SerpinB1 controls encephalitogenic T helper cells in neuroinflammation"],"prefix":"10.1073","volume":"116","author":[{"given":"Lifei","family":"Hou","sequence":"first","affiliation":[{"name":"The Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak A.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Yuki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Anesthesiology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cooley","sequence":"additional","affiliation":[{"name":"The Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"},{"name":"Division of Immunology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Helena","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion","family":"Kaiserman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Nigrovic","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology and Allergy, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"},{"name":"Division of Immunology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip I.","family":"Bird","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-7867","authenticated-orcid":false,"given":"Burkhard","family":"Becher","sequence":"additional","affiliation":[{"name":"Inflammation Unit, Institute of Experimental Immunology, University of Zurich, CH-8057 Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5197-1390","authenticated-orcid":false,"given":"Eileen","family":"Remold-O\u2019Donnell","sequence":"additional","affiliation":[{"name":"The Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Hematology\/Oncology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,9,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61620-7"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-009-9188-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.771"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01355"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.4.537"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00214.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041257"},{"key":"e_1_3_3_8_2","first-page":"61","article-title":"IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice","volume":"119","author":"Haak S.","year":"2009","unstructured":"S. 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