Characterization of Blimp-1 function in effector regulatory T cells

E Cretney, PSK Leung, S Trezise, DM Newman… - Journal of …, 2018 - Elsevier
E Cretney, PSK Leung, S Trezise, DM Newman, LC Rankin, CE Teh, TL Putoczki, DHD Gray
Journal of autoimmunity, 2018Elsevier
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+ …
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.
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