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c-Rel employs multiple mechanisms to promote the thymic development and peripheral function of regulatory T cells in mice.

Accepted version
Peer-reviewed

Type

Article

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Authors

Grumont, Raelene 
Wirasinha, Rushika C 
Ellis, Darcy 
Barugahare, Adele 

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.

Description

Keywords

Cell cycle progression, Regulatory T cells, Thymic development, c-Rel, Animals, Cell Differentiation, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Proto-Oncogene Proteins c-rel, T-Lymphocytes, Regulatory, Thymus Gland

Journal Title

Eur J Immunol

Conference Name

Journal ISSN

0014-2980
1521-4141

Volume Title

Publisher

Wiley

Rights

All rights reserved