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We previously showed that TNF-\u03b1 blockade during T cell stimulation in CD4+ T cell\/monocyte cocultures resulted in maintenance of IL-10\u2013producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4+ T cell\u2013only culture system. IL-10+ CD4+ T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10\u2013CD4+ T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3\/CD28 mAb\u2013mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. However, overexpression of IKZF3 was unable to upregulate IL-10 at the mRNA or protein level in CD4+ T cells and did not drive the transcription of the IL10 promoter or putative local enhancer constructs. Collectively, these data indicate that IKZF3 is associated with but not sufficient for IL-10 expression in CD4+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1901283","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T19:35:20Z","timestamp":1587584120000},"page":"2940-2948","source":"Crossref","is-referenced-by-count":22,"title":["IKZF3\/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4+ T Cells"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-2384","authenticated-orcid":false,"given":"Michael L","family":"Ridley","sequence":"first","affiliation":[{"name":"Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King\u2019s College London , London SE1 1UL ,","place":["United 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A","family":"Steel","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King\u2019s College London , London SE1 1UL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-651X","authenticated-orcid":false,"given":"Giovanni A M","family":"Povoleri","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King\u2019s College London , London SE1 1UL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, School of Immunology and Microbial Sciences, King\u2019s College London, Guy\u2019s Hospital , London SE1 9RT 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