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CD4+CD8+ double-positive thymocytes and thymic natural killer T cells in particular are highly sensitive to GICD. Although GICD is exploited via the use of synthetic GC analogues in the treatment of hematopoietic malignancies, the intracellular molecular pathway of GICD is not well understood. To explore GICD in thymocytes, the authors performed whole genome expression microarray analysis in mouse GR exon 2 null vs wild-type thymus RNA 3 hours after dexamethasone treatment. Identified and validated direct GR targets included P21 and Bim, in addition to an important transcriptional regulator Nfil3, which previously has been associated with GICD and is essential for natural killer cell development in vivo. Immunostaining of NFIL3 in whole thymus localized NFIL3 primarily to the medullary region, and double labeling colocalized NFIL3 to apoptotic cells. In silico analysis revealed a putative GC response element 5 kb upstream of the Nfil3 promoter that is strongly conserved in the rat genome and was confirmed to bind GR by chromatin immunoprecipitation. The knockdown of Nfil3 mRNA levels to 20% of normal using specific small interfering RNAs abrogated GICD, indicating that NFIL3 is required for normal GICD in CTLL-2 T cells.<\/jats:p>","DOI":"10.1210\/en.2012-1820","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T06:42:05Z","timestamp":1361428925000},"page":"1540-1552","source":"Crossref","is-referenced-by-count":21,"title":["Nfil3 Is a Glucocorticoid-Regulated Gene Required for Glucocorticoid-Induced Apoptosis in Male Murine T Cells"],"prefix":"10.1210","volume":"154","author":[{"given":"Kirstyn T.","family":"Carey","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology (K.T.C., K.H.T., J.N., D.R.L., T.J.C.), Monash University, Clayton, Victoria, 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kheng H.","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology (K.T.C., K.H.T., J.N., D.R.L., T.J.C.), Monash University, Clayton, Victoria, 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology (K.T.C., K.H.T., J.N., D.R.L., T.J.C.), Monash University, Clayton, Victoria, 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas R.","family":"Liddicoat","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology (K.T.C., K.H.T., J.N., D.R.L., T.J.C.), Monash University, Clayton, Victoria, 3800, Australia"},{"name":"Department of Immunology and Microbiology (D.R.L., D.I.G.), University of Melbourne, Parkville, Victoria, 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale I.","family":"Godfrey","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology (D.R.L., D.I.G.), University of Melbourne, Parkville, Victoria, 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology (K.T.C., K.H.T., J.N., D.R.L., T.J.C.), Monash University, Clayton, Victoria, 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613020291700_B1","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/j.1398-9995.2004.00635.x","article-title":"Glucocorticoid receptors in human airways","volume":"59","author":"Pujols","year":"2004","journal-title":"Allergy"},{"key":"2020071613020291700_B2","first-page":"55","article-title":"How do glucocorticoids influence stress responses? 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