Characterization of Blimp-1 function in effector regulatory T cells.

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