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Transcriptome landscape of double negative T cells by single-cell RNA sequencing
Yang, Lu5,6,7; Zhu, Yanbing3,4,5; Tian, Dan3,4,5; Wang, Song3,4,5; Guo, Jincheng2; Sun, Guangyong3,4,5; Jin, Hua3,4,5; Zhang, Chunpan3,4,5; Shi, Wen3,4,5; Gershwin, M. Eric1
刊名JOURNAL OF AUTOIMMUNITY
2021-07-01
卷号121页码:15
关键词Double negative T cell Single-cell RNA sequencing Unconventional T cells Inflammation Regulatory T cells Innate immunity
ISSN号0896-8411
DOI10.1016/j.jaut.2021.102653
英文摘要CD4 and CD8 coreceptor double negative TCR alpha beta+ T (DNT) cells are increasingly being recognized for their critical and diverse roles in the immune system. However, their molecular and functional signatures remain poorly understood and controversial. Moreover, the majority of studies are descriptive because of the relative low frequency of cells and non-standardized definition of this lineage. In this study, we performed single-cell RNA sequencing on 28,835 single immune cells isolated from mixed splenocytes of male C57BL/6 mice using strict fluorescence-activated cell sorting. The data was replicated in a subsequent study. Our analysis revealed five transcriptionally distinct nave DNT cell clusters, which expressed unique sets of genes and primarily performed T helper, cytotoxic and innate immune functions. Anti-CD3/CD28 activation enhanced their T helper and cytotoxic functions. Moreover, in comparison with CD4+, CD8+ T cells and NK cells, Ikzf2 was highly expressed by both nave and activated cytotoxic DNT cells. In conclusion, we provide a map of the heterogeneity in nave and active DNT cells, addresses the controversy about DNT cells, and provides potential transcription signatures of DNT cells. The landscape approach herein will eventually become more feasible through newer high throughput methods and will enable clustering data to be fed into a systems analysis approach. Thus the approach should become the "backdrop" of similar studies in the myriad murine models of autoimmunity, potentially highlighting the importance of DNT cells and other minor lineage of cells in immune homeostasis. The clear characterization of functional DNT subsets into helper DNT, cytotoxic DNT and innate DNT will help to better understand the intrinsic roles of different functional DNT subsets in the development and progression of autoimmune diseases and transplant rejection, and thereby may facilitate diagnosis and therapy.
资助项目National Natural Science Foundation of China[81570510] ; National Natural Science Foundation of China[81870399] ; National Natural Science Foundation of China[82001694]
WOS研究方向Immunology
语种英语
出版者ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号WOS:000663804000001
内容类型期刊论文
源URL[http://119.78.100.204/handle/2XEOYT63/17638]  
专题中国科学院计算技术研究所
通讯作者Gershwin, M. Eric; Zhang, Zhongtao; Zhao, Yi; Zhang, Dong
作者单位1.Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA
2.Chinese Acad Sci, Adv Comp Res Ctr, Inst Comp Technol, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China
3.Beijing Clin Res Inst, Beijing 100050, Peoples R China
4.Capital Med Univ, Beijing Friendship Hosp, Immunol Res Ctr Oral & Syst Hlth, Beijing, Peoples R China
5.Beijing Key Lab Tolerance Induct & Organ Protect, Beijing 100050, Peoples R China
6.Natl Clin Res Ctr Digest Dis, Beijing 100050, Peoples R China
7.Capital Med Univ, Beijing Friendship Hosp, Gen Surg Dept, Beijing 100050, Peoples R China
推荐引用方式
GB/T 7714
Yang, Lu,Zhu, Yanbing,Tian, Dan,et al. Transcriptome landscape of double negative T cells by single-cell RNA sequencing[J]. JOURNAL OF AUTOIMMUNITY,2021,121:15.
APA Yang, Lu.,Zhu, Yanbing.,Tian, Dan.,Wang, Song.,Guo, Jincheng.,...&Zhang, Dong.(2021).Transcriptome landscape of double negative T cells by single-cell RNA sequencing.JOURNAL OF AUTOIMMUNITY,121,15.
MLA Yang, Lu,et al."Transcriptome landscape of double negative T cells by single-cell RNA sequencing".JOURNAL OF AUTOIMMUNITY 121(2021):15.
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