Publications & Reports

The NF-kappaB transcription factor RelA is required for the tolerogenic function of Foxp3 regulatory T cells.

Messina N, Fulford T, O'Reilly L, Loh WX, Motyer JM, Ellis D, McLean C, Naeem H, Lin A, Gugasyan R, Slattery RM, Grumont RJ, Gerondakis S
Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.

Abstract

The properties of CD4+ regulatory T cell (Treg) subsets are dictated by distinct patterns of gene expression determined by FOXP3 and different combinations of various transcription factors. Here we show the NF-kappaB transcription factor RelA is constitutively active in naive and effector Tregs. The conditional inactivation of Rela in murine FOXP3+ cells induces a rapid onset, multi-focal autoimmune disease that depends on RelA being expressed in conventional T cells. In addition to promoting Treg lineage stability, RelA determines the size of the effector Treg population, a function influenced by the presence or absence of RelA in conventional T cells. These findings showing that RelA controls Treg stability and promotes the competitive fitness of effector Tregs highlight the importance of RelA activity in peripheral Treg induced tolerance.

Publication

  • Journal: Journal of Autoimmunity
  • Published: 07/04/2016
  • Volume: 70
  • Pagination: 52-62

Author