{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T02:16:51Z","timestamp":1776997011019,"version":"3.51.4"},"reference-count":51,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014364","name":"Samsung Science and Technology Foundation","doi-asserted-by":"publisher","award":["SSTF-BA1502-14"],"award-info":[{"award-number":["SSTF-BA1502-14"]}],"id":[{"id":"10.13039\/501100014364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1A2C3004006"],"award-info":[{"award-number":["NRF-2021R1A2C3004006"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A5A1015366"],"award-info":[{"award-number":["NRF-2017R1A5A1015366"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017H1A2A1042705"],"award-info":[{"award-number":["NRF-2017H1A2A1042705"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brain Korea 21"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,12,10]]},"abstract":"<jats:p>\n                    Central tolerance is achieved through positive and negative selection of thymocytes mediated by T cell receptor (TCR) signaling strength. Thus, dysregulation of the thymic selection process often leads to autoimmunity. Here, we show that Capicua (CIC), a transcriptional repressor that suppresses autoimmunity, controls the thymic selection process. Loss of CIC prior to T-cell lineage commitment impairs both positive and negative selection of thymocytes. CIC deficiency attenuated TCR signaling in CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    double-positive (DP) cells, as evidenced by a decrease in CD5 and phospho-ERK levels and calcium flux. We identified\n                    <jats:italic>Spry4<\/jats:italic>\n                    ,\n                    <jats:italic>Dusp4<\/jats:italic>\n                    ,\n                    <jats:italic>Dusp6,<\/jats:italic>\n                    and\n                    <jats:italic>Spred1<\/jats:italic>\n                    as CIC target genes that could inhibit TCR signaling in DP cells. Furthermore, impaired positive selection and TCR signaling were partially rescued in\n                    <jats:italic>Cic<\/jats:italic>\n                    and\n                    <jats:italic>Spry4<\/jats:italic>\n                    double mutant mice. Our findings indicate that CIC is a transcription factor required for thymic T cell development and suggests that CIC acts at multiple stages of T cell development and differentiation to prevent autoimmunity.\n                  <\/jats:p>","DOI":"10.7554\/elife.71769","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T08:00:24Z","timestamp":1639382424000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71769","source":"Crossref","is-referenced-by-count":25,"title":["Regulation of positive and negative selection and TCR signaling during thymic T cell development by capicua"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-0899","authenticated-orcid":true,"given":"Soeun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guk-Yeol","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyebeen","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-3087","authenticated-orcid":true,"given":"Yoontae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH)","place":["Pohang, Republic of Korea"]},{"name":"Institute of Convergence Science, Yonsei University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/onc.2008.464","article-title":"Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis","volume":"28","author":"Ayada","year":"2009","journal-title":"Oncogene"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1084\/jem.188.12.2301","article-title":"CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity","volume":"188","author":"Azzam","year":"1998","journal-title":"The Journal of Experimental Medicine"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1046\/j.1440-1711.1998.00709.x","article-title":"Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements","volume":"76","author":"Barnden","year":"1998","journal-title":"Immunology and Cell Biology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/1074-7613(95)90113-2","article-title":"A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection","volume":"3","author":"Calnan","year":"1995","journal-title":"Immunity"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1111\/j.1742-4658.2012.08716.x","article-title":"Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling","volume":"280","author":"Caunt","year":"2013","journal-title":"The FEBS Journal"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/nri2820","article-title":"Determining \u03b3\u03b4 versus \u03b1\u00df T cell development","volume":"10","author":"Ciofani","year":"2010","journal-title":"Nature Reviews. 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