IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4+ T Cells
Copyright © 2020 The Authors..
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-α 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:204 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 204(2020), 11 vom: 01. Juni, Seite 2940-2948 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ridley, Michael L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.03.2021 Date Revised 11.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.1901283 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4+ T Cells |
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| 520 | |a Copyright © 2020 The Authors. | ||
| 520 | |a 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-α 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 | ||
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| 700 | 1 | |a Roberts, Ceri A |e verfasserin |4 aut | |
| 700 | 1 | |a Lalnunhlimi, Sylvine |e verfasserin |4 aut | |
| 700 | 1 | |a Alnesf, Aldana |e verfasserin |4 aut | |
| 700 | 1 | |a O'Byrne, Aoife M |e verfasserin |4 aut | |
| 700 | 1 | |a Steel, Kathryn J A |e verfasserin |4 aut | |
| 700 | 1 | |a Povoleri, Giovanni A M |e verfasserin |4 aut | |
| 700 | 1 | |a Sumner, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Lavender, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Taams, Leonie S |e verfasserin |4 aut | |
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