Med1 Controls Effector CD8 + T Cell Differentiation and Survival through C/EBPβ-Mediated Transcriptional Control of T-bet.

Effector CD8 + T cells are crucial players in adaptive immunity for effective protection against invading pathogens. The regulatory mechanisms underlying CD8 + T cell effector differentiation are incompletely understood. In this study, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8 + T cell differentiation and survival during acute bacterial infection. Mice with Med1 -deficient CD8 + T cells exhibited significantly impaired expansion with evidently reduced killer cell lectin-like receptor G1 + terminally differentiated and Ly6c + effector cell populations. Moreover, Med1 deficiency led to enhanced cell apoptosis and expression of multiple inhibitory receptors (programmed cell death 1, T cell Ig and mucin domain-containing-3, and T cell immunoreceptor with Ig and ITIM domains). RNA-sequencing analysis revealed that T-bet- and Zeb2-mediated transcriptional programs were impaired in Med1 -deficient CD8 + T cells. Overexpression of T-bet could rescue the differentiation and survival of Med1 -deficient CD8 + effector T cells. Mechanistically, the transcription factor C/EBPβ 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 in response to bacterial infection.