Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 2006-2026 |
Number of pages | 21 |
Journal | European Journal of Immunology |
Volume | 51 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2021 |
Keywords
- c-Rel
- Cell cycle progression
- Regulatory T cells
- Thymic development
Projects
- 3 Finished
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How does NF-kB2 regulate thymic selection to prevent organ-specific autoimmune disease?
Daley, S.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/19
Project: Research
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Epigenetic regulation of lymphoid cell development and function
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/18
Project: Research
Equipment
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Bioinformatics Platform
Deanna Deveson (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility