NFAT公司
CD28
细胞生物学
转录因子
生物
信号转导
受体
下调和上调
T细胞
T细胞受体
分子生物学
化学
免疫系统
免疫学
基因
生物化学
作者
Annika De Sousa Linhares,Sumana Sharma,Peter Steinberger,Judith Leitner
出处
期刊:iScience
[Cell Press]
日期:2024-02-19
卷期号:27 (3): 109267-109267
被引量:2
标识
DOI:10.1016/j.isci.2024.109267
摘要
Costimulatory signals provided to T cells during antigen encounter have a decisive role in the outcome of immune responses. Here, we used chimeric receptors harboring the extracellular domain of mouse inducible T cell costimulator (mICOS) to study transcriptional activation mediated by cytoplasmic sequences of the major T cell costimulatory receptors CD28, 4-1BB, and CD2. The chimeric receptors were introduced in a T cell reporter platform that allows to simultaneously evaluate nuclear factor κB (NF-κB), NFAT, and AP-1 activation. Engagement of the chimeric receptors induced distinct transcriptional profiles. CD28 signaling activated all three transcription factors, whereas 4-1BB strongly promoted NF-κB and AP-1 but downregulated NFAT activity. CD2 signals resulted in the strongest upregulation of NFAT. Transcriptome analysis revealed pronounced and distinct gene expression signatures upon CD2 and 4-1BB signaling. Using the intracellular sequence of CD28, we exemplify that distinct signaling motifs endow chimeric receptors with different costimulatory capacities.
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