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

Authors :
Colby Zaph
David R. Powell
Paul A. Lyons
Thomas S Fulford
Sebastian Scheer
Kenneth G. C. Smith
Rushika C. Wirasinha
Raelene J. Grumont
Stephen R. Daley
Steve Gerondakis
Haroon Naeem
Ulf Klein
Stephen J. Turner
Darcy P. Ellis
Adele Barugahare
Fulford, Thomas S [0000-0002-7210-5739]
Lyons, Paul A [0000-0001-7035-8997]
Smith, Kenneth GC [0000-0003-3829-4326]
Apollo - University of Cambridge Repository
Source :
European journal of immunologyReferences. 51(8)
Publication Year :
2021

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. ispartof: EUROPEAN JOURNAL OF IMMUNOLOGY vol:51 issue:8 pages:2006-2026 ispartof: location:Germany status: published

Details

ISSN :
15214141 and 00142980
Volume :
51
Issue :
8
Database :
OpenAIRE
Journal :
European journal of immunologyReferences
Accession number :
edsair.doi.dedup.....08a99c971d5e8f71bac913ad00eb5020