{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:15:26Z","timestamp":1789265726387,"version":"build-2803163510"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inflammation that complicates many autoimmune diseases, such as multiple sclerosis (MS), has been correlated to abnormal differentiation of Th17 cells. However, the reasons that promote Th17 cell\u2013driven autoimmunity are yet to be discovered. In this study, we sought evidence that DNA-damage-inducible transcript 4 (DDIT4) and its associated long noncoding RNA DDIT4 (lncDDIT4) inhibit Th17 cell differentiation. We recruited 36 patients. Six MS patients and five healthy volunteers (controls) contributed PBMCs as material for microarray analysis. Microarray assays of lncDDIT4 and DDIT4 RNA expression identified outstanding differences between MS and control subjects, which were verified with real-time quantitative PCR. We then interrupted the expression of lncDDIT4 and DDIT4 mRNA in MS patients\u2019 naive CD4+ T cells and observed the resulting changes in Th17 cells. The expression of lncDDIT4 and DDIT4 mRNA were higher both in PBMCs and CD4+ T cells of MS patients than in healthy controls. DDIT4 (2.79-fold upregulation) was then recognized as a candidate for the cis-regulated target of lncDDIT4 (4.32-fold upregulation). Isolation of naive CD4+ T cells revealed enhanced levels of lncDDIT4 and DDIT4 after stimulated with Th17-inducing cytokines, but not after Th1, Th2, or T regulatory cell induction. Overexpression of lncDDIT4 in naive CD4+ T cells inhibited IL-17 transcription through increased DDIT4 expression and decreased activation of the DDIT4\/mTOR pathway. Consistently, silencing lncDDIT4 in naive CD4+ T cells enhanced Th17 differentiation through increased activation of the DDIT4\/mTOR pathway. However, these results vanished when DDIT4 was silenced. This outcome suggests that lncDDIT4 regulates Th17 cell differentiation by directly targeting DDIT4.<\/jats:p>","DOI":"10.4049\/jimmunol.1601689","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T19:30:23Z","timestamp":1517254223000},"page":"1618-1626","source":"Crossref","is-referenced-by-count":62,"title":["DDIT4 and Associated lncDDIT4 Modulate Th17 Differentiation through the DDIT4\/TSC\/mTOR Pathway"],"prefix":"10.1093","volume":"200","author":[{"given":"Fang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052,","place":["China"]},{"name":"School of Life Science and Technology, Harbin Institute of Technology , Harbin 150001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daojing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"2025030610020658800_r1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu. 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