Med1 Controls Effector CD8+ T Cell Differentiation and Survival through C/EBPβ-Mediated Transcriptional Control of T-bet
| Autor: | Anjun Jiao, Haiyan Liu, Renyi Ding, Huiqiang Zheng, Cangang Zhang, Zhao Feng, Lei Lei, Xin Wang, Yanhong Su, Xiaofeng Yang, Chenming Sun, Lianjun Zhang, Liang Bai, Lina Sun, Baojun Zhang |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 209:855-863 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2200037 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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