EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming

Area of Science:

• Immunology
• Epigenetics
• Cell Biology

Background:

• Memory CD8+ T cells are crucial for lifelong immunity.
• Naïve CD8+ T cells can acquire memory characteristics independent of foreign antigen exposure, influenced by cytokines like interleukin-4.
• This innate memory acquisition is linked to the transcription factor Eomesodermin (EOMES), but mechanisms are unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying the EOMES-driven acquisition of innate memory in CD8+ T cells.
• To investigate the role of epigenomic changes and chromatin remodeling in this process.

Main Methods:

• Epigenomic profiling of CD8+ T cells.
• Analysis of transcription factor recruitment (EOMES, RUNX3).
• Investigation of chromatin remodeling complexes involving BRG1.

Main Results:

• Innate memory CD8+ T cells exhibit a partial set of active enhancers compared to conventional memory cells.
• EOMES is recruited to RUNX3-bound enhancers, initiating epigenetic reprogramming.
• EOMES interacts with BRG1, a chromatin remodeler, and its recruitment is essential for EOMES-dependent programs in vivo.

Conclusions:

• EOMES plays a central role in establishing CD8+ T cell innate memory programs.
• Epigenetic modifications, particularly enhancer reprogramming mediated by EOMES and BRG1, are fundamental to this process.
• The findings provide a strong epigenetic basis for understanding innate CD8+ T cell memory development.