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学科主题: 基础医学
题名:
Smad4 represses the generation of memory-precursor effector T cells but is required for the differentiation of central memory T cells
作者: Cao, J.1; Zhang, X.1; Wang, Q.1; Qiu, G.1; Hou, C.1; Wang, J.1; Cheng, Q.1; Lan, Y.2; Han, H.3; Shen, H.4; Zhang, Y.5; Yang, X.2; Shen, B.1; Zhang, J.1
刊名: CELL DEATH & DISEASE
发表日期: 2015-11-01
DOI: 10.1038/cddis.2015.337
卷: 6, 期:0
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: TRANSCRIPTION FACTOR ; TRANSGENIC MICE ; EXPRESSION ; INFECTION ; FATES ; MAINTENANCE ; RESPONSES ; IMMUNITY ; SUBSETS ; DIRECTS
英文摘要:

The transcriptional regulation underlying the differentiation of CD8(+) effector and memory T cells remains elusive. Here, we show that 18-month-old mice lacking the transcription factor Smad4 (homolog 4 of mothers against decapentaplegic, Drosophila), a key intracellular signaling effector for the TGF-beta superfamily, in T cells exhibited lower percentages of CD44(hi)CD8(+) T cells. To explore the role of Smad4 in the activation/memory of CD8(+) T cells, 6- to 8-week-old mice with or without Smad4 in T cells were challenged with Listeria monocytogenes. Smad4 deficiency did not affect antigen-specific CD8(+) T-cell expansion but led to partially impaired cytotoxic function. Less short-lived effector T cells but more memory-precursor effector T cells were generated in the absence of Smad4. Despite that, Smad4 deficiency led to reduced memory CD8(+) T-cell responses. Further exploration revealed that the generation of central memory T cells was impaired in the absence of Smad4 and the cells showed survival issue. In mechanism, Smad4 deficiency led to aberrant transcriptional programs in antigen-specific CD8(+) T cells. These findings demonstrated an essential role of Smad4 in the control of effector and memory CD8(+) T-cell responses to infection.

语种: 英语
所属项目编号: 81472736 ; 31270960
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000367155300020
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68198
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
2.Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing, Peoples R China
3.Fourth Mil Med Univ, Dept Med Genet & Dev Biol, Xian 710032, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai Inst Immunol, Shanghai, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Minist Hlth, Key Lab Med Immunol, Beijing 100871, Peoples R China

Recommended Citation:
Cao, J.,Zhang, X.,Wang, Q.,et al. Smad4 represses the generation of memory-precursor effector T cells but is required for the differentiation of central memory T cells[J]. CELL DEATH & DISEASE,2015,6(0).
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