Characterization of Blimp-1 function in effector regulatory T cells

Abstract

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

Keywords: Blimp-1; Effector regulatory T cells; IL-10; Immune infiltration; Transcription.