气候变化领域集成服务门户(CCPortal): T cells selectively filter oscillatory signals on the minutes timescale

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DOI	10.1073/pnas.2019285118
	T cells selectively filter oscillatory signals on the minutes timescale
	O'Donoghue G.P.; Bugaj L.J.; Anderson W.; Daniels K.G.; Rawlings D.J.; Lim W.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	T cells experience complex temporal patterns of stimulus via receptor-ligand-binding interactions with surrounding cells. From these temporal patterns, T cells are able to pick out antigenic signals while establishing self-tolerance. Although features such as duration of antigen binding have been examined, our understanding of how T cells interpret signals with different frequencies or temporal stimulation patterns is relatively unexplored. We engineered T cells to respond to light as a stimulus by building an optogenetically controlled chimeric antigen receptor (optoCAR). We discovered that T cells respond to minute-scale oscillations of activation signal by stimulating optoCAR T cells with tunable pulse trains of light. Systematically scanning signal oscillation period from 1 to 150 min revealed that expression of CD69, a T cell activation marker, reached a local minimum at a period of ∼25 min (corresponding to 5 to 15 min pulse widths). A combination of inhibitors and genetic knockouts suggest that this frequency filtering mechanism lies downstream of the Erk signaling branch of the T cell response network and may involve a negative feedback loop that diminishes Erk activity. The timescale of CD69 filtering corresponds with the duration of T cell encounters with self-peptide-presenting APCs observed via intravital imaging in mice, indicating a potential functional role for temporal filtering in vivo. This study illustrates that the T cell signaling machinery is tuned to temporally filter and interpret time-variant input signals in discriminatory ways. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Cell signaling; Optogenetics; Signal transduction; Synthetic biology
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180470
作者单位	HHMI, University of California, San Francisco, CA 94158, United States; Department of Cellular and Molecular Pharmacology, Cell Design Institute, University of California, San Francisco, CA 94158, United States; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, United States; Department of Pediatrics, University of Washington, School of Medicine, Seattle, WA 98101, United States; Department of Immunology, University of Washington, School of Medicine, Seattle, WA 98101, United States; CERo Therapeutics, South San Francisco, CA 94080, United States; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	O'Donoghue G.P.,Bugaj L.J.,Anderson W.,et al. T cells selectively filter oscillatory signals on the minutes timescale[J],2021,118(9).
APA	O'Donoghue G.P.,Bugaj L.J.,Anderson W.,Daniels K.G.,Rawlings D.J.,&Lim W.A..(2021).T cells selectively filter oscillatory signals on the minutes timescale.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	O'Donoghue G.P.,et al."T cells selectively filter oscillatory signals on the minutes timescale".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).