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ECM resistance in<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>ANKA-infected<jats:italic>Themis<\/jats:italic><jats:sup>I23N<\/jats:sup>mice is associated with decreased cerebral cellular infiltration, retention of blood-brain barrier integrity, and reduced proinflammatory cytokine production. THEMIS<jats:sup>I23N<\/jats:sup>protein expression is absent from mutant mice, concurrent with the decreased THEMIS<jats:sup>I23N<\/jats:sup>stability observed<jats:italic>in vitro<\/jats:italic>. Biochemical studies<jats:italic>in vitro<\/jats:italic>and functional complementation<jats:italic>in vivo<\/jats:italic>in<jats:italic>Themis<\/jats:italic><jats:sup>I23N\/<jats:italic>+<\/jats:italic><\/jats:sup>:<jats:italic>Lck<\/jats:italic><jats:sup>\u2212\/<jats:italic>+<\/jats:italic><\/jats:sup>doubly heterozygous mice demonstrate that functional coupling of THEMIS to LCK tyrosine kinase is required for ECM pathogenesis. Damping of proinflammatory responses in<jats:italic>Themis<\/jats:italic><jats:sup>I23N<\/jats:sup>mice causes susceptibility to pulmonary tuberculosis. Thus, THEMIS is required for the development and ultimately the function of proinflammatory T cells.<jats:italic>Themis<\/jats:italic><jats:sup>I23N<\/jats:sup>mice can be used to study the newly discovered association of<jats:italic>THEMIS<\/jats:italic>(6p22.33) with inflammatory bowel disease and multiple sclerosis.<\/jats:p>","DOI":"10.1128\/iai.02586-14","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T08:05:56Z","timestamp":1417507556000},"page":"759-768","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["THEMIS Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis"],"prefix":"10.1128","volume":"83","author":[{"given":"Sabrina","family":"Torre","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, QC, Canada"},{"name":"Complex Traits Group, McGill University, Montreal, QC, 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