Résumé
The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent evidence indicates that lncRNAs possess higher lineage and stage specificity than mRNAs in T cell development, differentiation and function. However, the pivotal lncRNAs regulating CD8 T cell differentiation remain largely unclear. Through profiling of CD8 T cell lineages in this study, the lncRNA Snhg1 with the conserved on-off-on expression pattern in naïve-effector-memory CD8 T cells from mouse to human, is found to be required for memory CD8 T cell generation. Further, Snhg1 is found interacting with the highly conserved vesicle trafficking protein Vps13D to facilitate IL-7Rα membrane location specifically. IL-7 has been reported to sustain memory survival through STAT5-BCL2 axis, but whether IL-7 can directly promote memory differentiation remain cloudy. In this research, Snhg1/Vps13D depletion impair memory formation through IL-7-STAT3-TCF1-Blimp1 axis. Whether TCF-1 is induced by canonical Wnt-β-Catenin signaling in memory CD8 generation remain controversial. This work finds gene Tcf7 is regulated by direct binding of p-STAT3 in CD8 stimulated with IL-7. Furthermore, TCF-1 is found promoting memory with blocking effector mainly through impeding Prdm1 expression directly to balance Blimp1-BCL6 and Blimp1-ID3 axis. Thus, this study proposes a model for lncRNA as critical factor that couples membrane trafficking of cytokine receptor with transcriptional induction to promote memory CD8 T cell establishment.