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Abstract

The expression of anti-inflammatory IL-10 by CD4 + T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-a blockade during T cell stimulation in CD4 + T cell/monocyte cocultures resulted in maintenance of IL-10–producing 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–only culture system. IL-10 + CD4 + T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10–CD4 + T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb–mediated 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.

Original languageEnglish
Pages (from-to)2940-2948
Number of pages9
JournalJournal of Immunology
Volume204
Issue number11
Early online date22 Apr 2020
DOIs
Publication statusPublished - 1 Jun 2020

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