Affordable Access

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

Authors
  • Fulford, Thomas S
  • Grumont, Raelene
  • Wirasinha, Rushika C
  • Ellis, Darcy
  • Barugahare, Adele
  • Turner, Stephen J
  • Naeem, Haroon
  • Powell, David
  • Lyons, Paul A
  • Smith, Kenneth GC
  • Scheer, Sebastian
  • Zaph, Colby
  • Klein, Ulf
  • Daley, Stephen R
  • Gerondakis, Steve
Publication Date
Aug 01, 2021
Source
Apollo - University of Cambridge Repository
Keywords
Language
English
License
Unknown
External links

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.

Report this publication

Statistics

Seen <100 times