Identification of p-eIF4E as a new regulator of regulatory T-cell activity

Abstract Objective: Phosphorylated Eukaryotic translation initiation factor 4E (p-eIF4E) is a critical regulator of protein synthesis and phosphorylated by MNK1/2 to promote the mRNA subset. We have shown that blocking eIF4E phosphorylation increased anti-tumor immune response, especially CD8 T cell activation. However, role p-eIF4E in CD4 subsets, particular regulatory cells (Tregs) still unknown. The aim this study was explore impact absence could on Treg activity as well an inflammatory context. Methods: To investigate Tregs activity, we used genetically modified mice expressing non-phosphorylatable form (KI mice). First, analyzed WT KI same subjected dextran sulfate sodium (DSS)-induced colitis. also colonic infiltration using spectral flow cytometry CODEX technology. Results: Using our mouse models, observed lack led decrease stability their ability control helper (Th) proliferation. In colitis context, increase disease severity compared characterized infiltration. Moreover, mesenteric lymph node colon immunophenotyping revealed significant Treg, Th IFNγ mice. Finally, migrate nodes. Conclusion: These results demonstrate for first time preponderant migration but regulate inflammation.