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IKZF3/Aiolos is associated with, but not sufficient for the expression of IL-10 by CD4+ T cells: IKZF3 is associated with IL-10+ CD4+ T cells

Research output: Contribution to journalArticle

Original languageEnglish
JournalJ. Immunol
Early online date22 Apr 2020
DOIs
Publication statusE-pub ahead of print - 22 Apr 2020

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  • 19-01283-FLR_R2_Taams 020420 for PURE

    19_01283_FLR_R2_Taams_020420_for_PURE.pdf, 3.07 MB, application/pdf

    23/04/2020

    Accepted author manuscript

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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 TNFα blockade during T cell stimulation in CD4+ T cell/monocyte co-cultures resulted in maintenance of IL-10 producing T cells and identified IKZF3 as a putative regulator of IL-10. Here, 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 to 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.

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