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

par Istaces, Nicolas ;Splittgerber, Marion ;Lima Silva, Viviana ;Nguyen, Muriel ;Thomas, Séverine ;Le, Aurore ;Achouri, Younes ;Calonne, Emilie ;Defrance, Matthieu ;Fuks, François ;Goriely, Stanislas ;Azouz, Abdulkader
Référence Nature communications, 10, 1, 3306
Publication Publié, 2019-10-01

Article révisé par les pairs

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Résumé :

Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.