HIVEP3 inhibits fate decision of CD8+ invariant NKT cells after positive selection

Author:

Wu Qielan12ORCID,Bai Shiyu12,Su Miya12,Zhang Yuwei12,Chen Xuran12,Yue Ting2,Xu Linfeng2,Wang Lu3,Xie Di12,Li Shuhang12,Li Xiang12ORCID,Fu Sicheng12,Wang Lili12,Tian Chenxi12,Pan Jun12,Huang Yuanyuan12,Cai Yuting12,Wang Yu12,Hu Fang12,Li Fengyin12,Zhang Huimin12,Bai Li1245

Affiliation:

1. Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China , No. 443 Huangshan Street, Shushan District, Hefei 230027 , China

2. Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China , No. 443 Huangshan Street, Shushan District, Hefei 230027 , China

3. Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , No. 160 Pujian Road, Pudong Disctrict, Shanghai 200127 , China

4. Institute of Health and Medicine, Hefei Comprehensive National Science Center , 4090 Susong Road, Shushan District, Hefei 230601 , China

5. National Synchrotron Radiation Laboratory, University of Science and Technology of China , No. 443 Huangshan Street, Shushan District, Hefei 230027 , China

Abstract

Abstract CD8+ invariant natural killer T (iNKT) cells are functionally different from other iNKT cells and are enriched in human but not in mouse. To date, their developmental pathway and molecular basis for fate decision remain unclear. Here, we report enrichment of CD8+ iNKT cells in neonatal mice due to their more rapid maturation kinetics than CD8− iNKT cells. Along developmental trajectories, CD8+ and CD8− iNKT cells separate at stage 0, following stage 0 double-positive iNKT cells, and differ in HIVEP3 expression. HIVEP3 is lowly expressed in stage 0 CD8+ iNKT cells and negatively controls their development, whereas it is highly expressed in stage 0 CD8− iNKT cells and positively controls their development. Despite no effect on IFN-γ, HIVEP3 inhibits granzyme B but promotes interleukin-4 production in CD8+ iNKT cells. Together, we reveal that, as a negative regulator for CD8+ iNKT fate decision, low expression of HIVEP3 in stage 0 CD8+ iNKT cells favors their development and T helper 1–biased cytokine responses as well as high cytotoxicity.

Funder

National Key R&D Program of China

National Natural Science Foundation of China

University Synergy Innovation Program of Anhui Province

Natural Science Foundation of Hefei

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Immunology,Immunology and Allergy

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3