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

• Published in: The Journal of immunology (1950) 2022-09, Vol.209 (5), p.855-863
• Main Authors: Jiao, Anjun, Liu, Haiyan, Ding, Renyi, Zheng, Huiqiang, Zhang, Cangang, Feng, Zhao, Lei, Lei, Wang, Xin, Su, Yanhong, Yang, Xiaofeng, Sun, Chenming, Zhang, Lianjun, Bai, Liang, Sun, Lina, Zhang, Baojun
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2200037

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.