c-Rel employs multiple mechanisms to promote the thymic development and peripheral function of regulatory T cells in mice
Description
The NF-κB transcription factor c-Rel is a critical regulator of Treg ontogeny, controlling multiple points of the stepwise developmental pathway. Here, we found that the thymic Treg defect in c-Rel-deficient (cRel–/–) mice is quantitative, not qualitative, based on analyses of TCR repertoire and TCR signaling strength. However, these parameters are altered in the thymic Treg-precursor population, which is also markedly diminished in cRel–/– mice. Moreover, c-Rel governs the transcriptional programme of both thymic and peripheral Tregs, controlling a core of genes involved with immune signaling, and separately in the periphery, cell cycle progression. Last, the immune suppressive function of peripheral cRel–/– tTregs is diminished in a lymphopenic model of T cell proliferation and is associated with decreased stability of Foxp3 expression. Collectively, we show that c-Rel is a transcriptional regulator that controls multiple aspects of Treg development, differentiation, and function via distinct mechanisms.
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ID Code: | 212675 | ||
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Item Type: | Contribution to Journal (Journal Article) | ||
Refereed: | Yes | ||
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Additional Information: | Funding Information: We thank Eric Huseby (University of Massachusetts Medical School), Stephen Nutt (Walter and Eliza Hall Institute of Medical Research) and Kristin Hogquist (University of Minnesota) for the respective gifts of Yae62β‐tg, Blimp and Nur77 mice, and the staff of Monash Animal Research Platform and FlowCore for technical assistance. This research was supported by the Monash Biomedicine Discovery Institute and by the NHMRC Grant 1107464 to SRD; veski Innovation Fellowship and NHMRC Project Grants 1104433 and 1104466 to CZ; NIH/NCI Grant R01 CA157660 to UK; and NHMRC Principal Research Fellowship awarded to SJT. The authors acknowledge use of the services and facilities of Micromon Genomics at Monash University. Graphical abstract created with BioRender.com. We also thank Adam Uldrich for constructive feedback and advice. gfp gfp | ||
Measurements or Duration: | 21 pages | ||
Additional URLs: | |||
Keywords: | c-Rel, Cell cycle progression, Regulatory T cells, Thymic development | ||
DOI: | 10.1002/eji.202048900 | ||
ISSN: | 0014-2980 | ||
Pure ID: | 96887183 | ||
Funding Information: | We thank Eric Huseby (University of Massachusetts Medical School), Stephen Nutt (Walter and Eliza Hall Institute of Medical Research) and Kristin Hogquist (University of Minnesota) for the respective gifts of Yae62β‐tg, Blimp and Nur77 mice, and the staff of Monash Animal Research Platform and FlowCore for technical assistance. This research was supported by the Monash Biomedicine Discovery Institute and by the NHMRC Grant 1107464 to SRD; veski Innovation Fellowship and NHMRC Project Grants 1104433 and 1104466 to CZ; NIH/NCI Grant R01 CA157660 to UK; and NHMRC Principal Research Fellowship awarded to SJT. The authors acknowledge use of the services and facilities of Micromon Genomics at Monash University. Graphical abstract created with BioRender.com. We also thank Adam Uldrich for constructive feedback and advice. gfp gfp We thank Eric Huseby (University of Massachusetts Medical School), Stephen Nutt (Walter and Eliza Hall Institute of Medical Research) and Kristin Hogquist (University of Minnesota) for the respective gifts of Yae62?-tg, Blimpgfp and Nur77gfp mice, and the staff of Monash Animal Research Platform and FlowCore for technical assistance. This research was supported by the Monash Biomedicine Discovery Institute and by the NHMRC Grant 1107464 to SRD; veski Innovation Fellowship and NHMRC Project Grants 1104433 and 1104466 to CZ; NIH/NCI Grant R01 CA157660 to UK; and NHMRC Principal Research Fellowship awarded to SJT. The authors acknowledge use of the services and facilities of Micromon Genomics at Monash University. Graphical abstract created with BioRender.com. We also thank Adam Uldrich for constructive feedback and advice. | ||
Copyright Owner: | © 2021 Wiley-VCH GmbH. | ||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
Deposited On: | 18 Aug 2021 23:23 | ||
Last Modified: | 29 Feb 2024 11:33 |
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