{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:28:59Z","timestamp":1781620139414,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT 1022922"],"award-info":[{"award-number":["GNT 1022922"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the effect of DOCK8 deficiency on thymic tolerance in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thymocytes from wild\u2010type (<jats:italic>Dock8<jats:sup>+\/+<\/jats:sup><\/jats:italic>) and DOCK8\u2010deficient (<jats:italic>Dock8<jats:sup>pri\/pri<\/jats:sup><\/jats:italic>) mice were examined by flow cytometry. Some mice had transgenic expression of the BCL2 anti\u2010apoptotic protein in haemopoietic cells. Some mice expressed the transgenic 3A9 T\u2010cell receptor (TCR), which triggers thymocyte deletion in mice also expressing hen egg lysozyme under the insulin promoter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In <jats:italic>Dock8<jats:sup>pr\/pri<\/jats:sup><\/jats:italic> mice, the proportion of thymocytes induced to acquire tolerance at the immature CCR7<jats:sup>\u2212<\/jats:sup> stage was normal. Deletion of strongly self\u2010reactive CD4<jats:sup>+<\/jats:sup> thymocytes occurred efficiently in <jats:italic>Dock8<jats:sup>pri\/pri<\/jats:sup><\/jats:italic> mice in a TCR\u2010transgenic model that requires self\u2010antigen transfer from epithelial cells to bone marrow (BM)\u2010derived antigen\u2010presenting cells. Thymic Foxp3<jats:sup>+<\/jats:sup> T\u2010regulatory cells (T<jats:sub>REG<\/jats:sub>) and Helios<jats:sup>+<\/jats:sup> Foxp3<jats:sup>\u2212<\/jats:sup> T<jats:sub>REG<\/jats:sub> precursors were decreased in <jats:italic>Dock8<jats:sup>pri\/pri<\/jats:sup><\/jats:italic> mice, including when apoptosis was inhibited by BCL2 transgene expression. <jats:italic>Dock8<jats:sup>pri\/pri<\/jats:sup><\/jats:italic> thymic T<jats:sub>REG<\/jats:sub> expressed CD25 and CTLA\u20104 at normal levels. The results suggest that DOCK8 deficiency does not affect the function of BM\u2010derived antigen\u2010presenting cells in the thymus, the TCR self\u2010reactivity threshold that activates tolerance mechanisms in thymocytes or the apoptotic deletion of these thymocytes. However, DOCK8 is required to prevent a subset of developing T<jats:sub>REG<\/jats:sub> cells from undergoing cell death via a mechanism that is distinct from apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DOCK8 deficiency diminishes T<jats:sub>REG<\/jats:sub> development in the thymus without compromising thymocyte deletion.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1236","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T21:50:24Z","timestamp":1610488224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["DOCK8 deficiency diminishes thymic T\u2010regulatory cell development but not thymic deletion"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-6020","authenticated-orcid":false,"given":"Katrina L","family":"Randall","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases The John Curtin School of Medical Research The Australian National University Canberra ACT Australia"},{"name":"Australian National University Medical School The Australian National University Canberra ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsei Di","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases The John Curtin School of Medical Research The Australian National University Canberra ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F","family":"Ziolkowski","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases The John Curtin School of Medical Research The Australian National University Canberra ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rushika C","family":"Wirasinha","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-6155","authenticated-orcid":false,"given":"Christopher C","family":"Goodnow","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research &amp; Cellular Genomics Futures Institute University of New South Wales Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-644X","authenticated-orcid":false,"given":"Stephen R","family":"Daley","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905506"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.038"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0126-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110345"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1820"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141307"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-407098"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12723"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.042"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94298"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12532"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121458"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.021"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94275"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85774"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0331-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.14943"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.95"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.38"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0289-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.022"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3150"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.003"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020735"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12904"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-482331"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141759"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2105"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1539"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80528-2"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1236","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1236","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T09:41:13Z","timestamp":1693734073000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/cti2.1236"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1236","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1236"}}