King's College London

Research portal

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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2940-2948
Number of pages9
JournalJ. Immunol
Volume204
Issue number11
Early online date22 Apr 2020
DOIs
Accepted/In press2 Apr 2020
E-pub ahead of print22 Apr 2020
Published1 Jun 2020

Documents

  • 19-01283-FLR_R2_Taams 020420 for PURE

    19_01283_FLR_R2_Taams_020420_for_PURE.pdf, 3.07 MB, application/pdf

    Uploaded date:23 Apr 2020

    Version:Accepted author manuscript

    Licence:CC BY

    Authors who wish to make their article freely available immediately upon publication in The Journal of Immunology may utilize the Author Choice option. In addition to being made freely available on The Journal of
    Immunology web site immediately upon publication, AAI will deposit the published version of Author Choice articles into PubMed Central for immediate posting there as well as on the PMC mirror sites (UKPMC and PMC
    Canada).

    The Author Choice option is available for $2,500 to Corresponding Authors who are Regular, Emeritus or
    Honorary AAI members on the date of manuscript acceptance. The Author Choice fee is in addition to other Publication Fees. By indicating that you choose the Author Choice option, you are agreeing to incur the cost of this service.

    YES, as Corresponding Author I agree to pay the Author Choice option in addition to other Publication Fees.

King's Authors

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.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454