{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:35:40Z","timestamp":1782938140395,"version":"3.54.5"},"reference-count":52,"publisher":"The Royal Society","issue":"2","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["100140"],"award-info":[{"award-number":["100140"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007492","name":"Bettencourt Schueller Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>\n                    Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, T-cell receptor (TCR) engagement drives a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs. To gain a better insight into this mechanism, we compared the transcriptional profiles of naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to those of activated CTLs. To find new regulators of CTL function, we performed a selective clustered regularly interspaced short palindromic repeats (CRISPR) screen on upregulated genes and identified nuclear factor IL-3 (NFIL3) as a potential regulator of cytotoxicity. Although NFIL3 has established roles in several immune cells including natural killer, Treg, dendritic and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, its function in CD8\n                    <jats:sup>+<\/jats:sup>\n                    CTLs is less well understood. Using CRISPR\/Cas9 editing, we found that removing NFIL3 in CTLs resulted in a marked decrease in cytotoxicity. We found that in CTLs lacking NFIL3 TCR-induced extracellular signal-regulated kinase phosphorylation, immune synapse formation and granule release were all intact while cytotoxicity was functionally impaired\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Strikingly, NFIL3 controls the production of cytolytic proteins as well as effector cytokines. Thus, NFIL3 plays a cell intrinsic role in modulating cytolytic mechanisms in CTLs.\n                  <\/jats:p>","DOI":"10.1098\/rsob.230456","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T19:05:39Z","timestamp":1709060739000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["NFIL3 contributes to cytotoxic T lymphocyte-mediated killing"],"prefix":"10.1098","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-8358","authenticated-orcid":true,"given":"Tiphaine","family":"Douanne","sequence":"first","affiliation":[{"name":"Cambridge Institute for Medical Research, Keith Peters Building, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Strege","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, Keith Peters Building, Cambridge CB2 0XY, UK"},{"name":"Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Del Castillo Velasco-Herrera","sequence":"additional","affiliation":[{"name":"Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-1206","authenticated-orcid":true,"given":"Adam M.","family":"Rochussen","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, Keith Peters Building, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0434-5842","authenticated-orcid":true,"given":"Gillian M.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, Keith Peters Building, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3031"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0495-x"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.186205"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.013"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710751114"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00234-5"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05071"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-45"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0009-3"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.11.6055"},{"key":"e_1_3_9_13_2","first-page":"3070","article-title":"Transcriptional repression by a novel member of the bZIP family of transcription factors","volume":"12","author":"Cowell IG","year":"1992","unstructured":"Cowell IG, Skinner A, Hurst HC. 1992 Transcriptional repression by a novel member of the bZIP family of transcription factors. 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