{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:31:06Z","timestamp":1778754666271,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Impaired proliferation and production of IL2 are the hallmarks of experimental T cell tolerance. However, in most autoimmune diseases, auto\u2010reactive T cells do not display hyper proliferation, but inflammatory phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have now demonstrated that the transcription factors Egr2 and 3 are important for the control of inflammatory cytokine production by tolerant T cells, but not for tolerance induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the absence of Egr2 and 3, T cell tolerance, as measured by impaired proliferation and production of IL2, can still be induced, but tolerant T cells produced high levels of inflammatory cytokines. Egr2 and 3 regulate expression of differentiation repressors and directly inhibit T\u2010bet function in T cells. Indeed, decreased expression of differentiation repressors, such as Id3 and Tcf1, and increased expression of inflammatory transcription factors, such as ROR\u03b3t and Bhlhe40 were found in Egr2\/3 deficient T cells under tolerogenic conditions. In addition, T\u2010bet was co\u2010expressed with Egr2 in tolerant T cells and Egr2\/3 defects leads to production of high levels of IFN\u03b3 in tolerant T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings demonstrated that despite impaired proliferation and IL2 production, tolerant T cells can display inflammatory responses in response to antigen stimulation and this is controlled at least partly by Egr2 and 3.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.210","type":"journal-article","created":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T04:03:20Z","timestamp":1515038600000},"page":"221-233","source":"Crossref","is-referenced-by-count":13,"title":["Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells"],"prefix":"10.1002","volume":"6","author":[{"given":"Becky","family":"Omodho","sequence":"first","affiliation":[{"name":"The Blizard Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London 4 Newark Street, London UK"},{"name":"Bioscience Brunel University London Kingston Lane, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tizong","family":"Miao","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London 4 Newark Street, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-0816","authenticated-orcid":false,"given":"Alistair L.J.","family":"Symonds","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London 4 Newark Street, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Bioscience Brunel University London Kingston Lane, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suling","family":"Li","sequence":"additional","affiliation":[{"name":"Bioscience Brunel University London Kingston Lane, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London 4 Newark Street, London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141623"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141110"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3307"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78087"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.04.006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2007.02586.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200635883"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7331"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1193"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080187"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611286114"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602010"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160553"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312398200"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","unstructured":"Pohlert T.2014. 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