GSE193624
Med1 controls effector CD8+ T cell differentiation and survival through mediating the transcriptional regulation of C/EBPß on T-bet
Effector CD8+ T cells are crucial in adaptive immunity for effective protection against infectious pathogens. The regulatory mechanisms underlying CD8+ effector T cell development are incompletely understood. Here, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8+ T cell differentiation and survival during acute infections. Mice with Med1 deletion in CD8+ T cells exhibited a significantly impaired effector cell expansion with large reduction of KLRG1+ terminally differentiated and Ly6c+ effector cell populations. Med1 deficiency led to enhanced cell apoptosis and expression of exhausted T cell associated inhibitory receptors (PD-1, Tim3, Lag3 and TIGHT). RNA-Seq analysis revealed the defects of T-bet and Zeb2 mediated transcriptional programs in effector differentiation. Overexpression of T-bet could rescue the Med1-deficient CD8+ effector T cell differentiation and survival. Mechanistically, transcription factor C/EBPß promoted T-bet expression through interacting with Med1 in effector T cells. Collectively, our findings revealed a novel role of Med1 in regulating effector CD8+ T cell differentiation and survival during immune response. Overall design: WT and KO CD8+ T cells were sorted from the spleens of recipient mice 7 days after LM-OVA infection in the co-transfer model.