Smad4 represses the generation of memory-precursor effector T cells but is required for the differentiation of central memory T cells.
Smad4 represses the generation of memory-precursor effector T cells but is required for the differentiation of central memory T cells.
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Smad4 抑制记忆前体效应 T 细胞的生成，但是中央记忆 T 细胞分化所必需的
DOI：
10.1038/cddis.2015.337
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发表时间：
2015-11-19
影响因子：
9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Cao J;Zhang X;Wang Q;Qiu G;Hou C;Wang J;Cheng Q;Lan Y;Han H;Shen H;Zhang Y;Yang X;Shen B;Zhang J
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-β 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.
