Characterization of Blimp-1 function in effector regulatory T cells Academic Article uri icon

abstract

  • Regulatory T (Treg) cells maintain immunological tolerance in steady-state and after immune challenge. Activated Treg cells can undergo further differentiation into an effector state that highly express genes critical for Treg cell function, including ICOS, TIGIT and IL-10, although how this process is controlled is poorly understood. Effector Treg cells also specifically express the transcriptional regulator Blimp-1 whose expression overlaps with many of the canonical markers associated with effector Treg cells, although not all ICOS+TIGIT+ Treg cells express Blimp-1 or IL-10. In this study, we addressed the role of Blimp-1 in effector Treg cell function. Mice lacking Blimp-1 specifically in Treg cells mature normally, but succumb to a multi-organ inflammatory disease later in life. Blimp-1 is not required for Treg cell differentiation, with mutant mice having increased numbers of effector Treg cells, but regulated a suite of genes involved in cell signaling, communication and survival, as well as being essential for the expression of the immune modulatory cytokine IL-10. Thus, Blimp-1 is a marker of effector Treg cells in all contexts examined and is required for the full functionality of these cells during aging.

authors

  • Cretney, Erika
  • Leung, Patrick SK
  • Trezise, Stephanie
  • Newman, Dane M
  • Rankin, Lucille C
  • Teh, Charis E
  • Putoczki, Tracy L
  • Gray, Daniel HD
  • Belz, Gabrielle T
  • Mielke, Lisa A
  • Dias, Sheila
  • Nutt, Stephen L

publication date

  • 2018