期刊
SCIENCE
卷 375, 期 6580, 页码 513-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abj4008
关键词
-
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [DP3DK111914-01]
- Simons Foundation
- Burroughs Wellcome Fund, Career Award for Medical Scientists
- Cancer Research Institute Lloyd J. Old STAR grant
- Parker Institute for Cancer Immunotherapy
- Innovative Genomics Institute
- National Institutes of Health [R01HG008140, S10 RR028962, P30 DK063720, S10 1S10OD021822-01]
- Parker Institute for Cancer Immunology scholarship
- Austrian Exchange Service Fellowship
- Austrian Society of Laboratory Medicine Fellowship
- James B. Pendleton Charitable Trust
- Max Kade Foundation
- Care-for-Rare Foundation
- German Research Foundation
This study conducted gene screening using CRISPR technology in primary human T cells, identifying gene networks that regulate the production of interleukin-2 and interferon-gamma. It revealed reshaped cytokine responses and the mechanisms of T cell activation, providing new insights for designing immunotherapies.
Regulation of cytokine production in stimulated T cells can be disrupted in autoimmunity, immunodeficiencies, and cancer. Systematic discovery of stimulation-dependent cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now report genome-wide CRISPR activation (CRISPRa) and interference (CRISPRi) screens in primary human T cells to identify gene networks controlling interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production. Arrayed CRISPRa confirmed key hits and enabled multiplexed secretome characterization, revealing reshaped cytokine responses. Coupling CRISPRa screening with single-cell RNA sequencing enabled deep molecular characterization of screen hits, revealing how perturbations tuned T cell activation and promoted cell states characterized by distinct cytokine expression profiles. These screens reveal genes that reprogram critical immune cell functions, which could inform the design of immunotherapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据