Characterization of Blimp-1 function in effector regulatory T cells

Publication date: Available online 30 April 2018
Source:Journal of Autoimmunity
Author(s): Erika Cretney, Patrick SK. Leung, Stephanie Trezise, Dane M. Newman, Lucille C. Rankin, Charis E. Teh, Tracy L. Putoczki, Daniel HD. Gray, Gabrielle T. Belz, Lisa A. Mielke, Sheila Dias, Stephen L. Nutt
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.



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