Med1 Controls Effector CD8+ T Cell Differentiation and Survival through C/EBP β-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 Medl-deficient CD8(+) effector T cells. Mechanistically, the transcription factor C/EBP beta 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.

Automated summary

This study demonstrates the crucial role of mediator complex subunit 1 (Med1) in controlling effector CD8(+) T cell differentiation and survival during acute bacterial infection. Med1 deficiency leads to impaired expansion, reduced terminally differentiated and effector cell populations, enhanced cell apoptosis, and increased expression of inhibitory receptors. The transcriptional programs mediated by T-bet and Zeb2 are impaired in Med1-deficient CD8(+) T cells. Overexpression of T-bet can rescue the differentiation and survival of Med1-deficient CD8(+) effector T cells. Mechanistically, the transcription factor C/EBP beta promotes T-bet expression through interacting with Med1 in effector T cells.