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The m1A modification of tRNAs:a translational accelerator of T-cell activation

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Cellular & Molecular Immunology 2022年第12期19卷 1328-1329页

作者： Cheng Chen Lilin Ye Institute of Immunology Third Military Medical UniversityChongqing400038China

Upon antigen stimulation,naïve T cells exit the quiescent state and undergo rapid clonal expansion and differentiation[1].This cell fate transition requires accelerated protein synthesis,which is regulated at both the transcriptional and translational levels[2,3].Compared with well-documented transcriptional regulatory mechanisms,the translational regulation of T-cell activation has not been fully elucidated.A recent study by Liu et al.

关键词： activation translational accelerator

TFH and TFR Fate Commitments

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TFH and TFR Fate Commitments

Efficient control of chronic LCMV infection by a CD4 T cell epitope-based heterologous prime-boost vaccination in a murine model

第十三届全国免疫学学术大会

作者： Lilin Ye PLA Institute of Immunology Third Military Medical University

Follicular helper T cells (TFH) play important role in humoral immunity by initiating and maintaining germinal center reactions and driving GC B cells to differentiate into plasma cells and memory B cells. Bcl6, a transcription repressor, is necessary and sufficient to drive TFH differentiation, by contrast, Blimp1, a transcription factor, inhibits TFH differentiation. Thus, Bcl6-Blimp1 balance dictates TFH differentiation fates. However, how such balance is regulated for optimal

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Cellular & Molecular Immunology 2018年第9期15卷 815-826页

作者： Ran He Xinxin Yang Cheng Liu Xiangyu Chen Lin Wang Minglu Xiao Jianqiang ye Yuzhang Wu Lilin Ye Center for Clinical Laboratory Zhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Institute of Immunology Medical SchoolThird Military Medical UniversityChongqing 400038China Ministry of Education Key Laboratory for Avian Preventive Medicine College of Veterinary MedicineYangzhou UniversityYangzhouJiangsu 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses YangzhouJiangsu 225009China

CD4^(+)T cells are essential for sustaining CD8^(+)T cell responses during a chronic infection.The adoptive transfer of virus-specific CD4^(+)T cells has been shown to efficiently rescue exhausted CD8^(+)T cells.However,the question of whether endogenous virus-specific CD4^(+)T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8^(+)T cells remains unexplored.In this study,we developed a CD4^(+)T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus(LCMV)infection.We primed chronically LCMV-infected mice with a Listeria monocytogenes vector that expressed the LCMV glycoprotein-specific I-Ab-restricted CD4^(+)T cell epitope GP61–80(LM-GP61)and subsequently boosted the primed mice with an influenza virus A(PR8 strain)vector that expressed the same CD4^(+)T cell epitope(IAV-GP61).This heterologous prime-boost vaccination strategy elicited strong anti-viral CD4^(+)T cell responses,which further improved both the quantity and quality of the virusspecific CD8^(+)T cells and led to better control of the viral loads.The combination of this strategy and the blockade of the programmed cell death-1(PD-1)inhibitory pathway further enhanced the anti-viral CD8^(+)T cell responses and viral clearance.Thus,a heterologous prime-boost immunization that selectively induces virus-specific CD4^(+)T cell responses in conjunction with blockade of the inhibitory pathway may represent a promising therapeutic approach to treating patients with chronic viral infections.

关键词： CD4^(+)T cell epitope CD8^(+)T cell exhaustion chronic viral infection prime-boost

CD49a^(+)CD49b^(+) NK cells induced by viral infection reflect an activated state of conventional NK cells

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Science China(Life Sciences) 2020年第11期63卷 1725-1733页

作者： Wenhan Li Jing Zhou Xianwei Wang Yuzhang Wu Lilin Ye Haiming Wei Rui Sun Zhigang Tian Hui Peng Division of Molecular Medicine Hefei National Laboratory for Physical Sciences at Microscalethe CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Institue of Immunology University of Science and Technology of ChinaHefei 230027China Institute of Immunology Third Military Medical UniversityChongqing 400038China

Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK cells.Here, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a^(+)CD49b^(+) NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection,before progressively decreasing in cell number. These viral infection-induced CD49a^(+)CD49b^(+) NK cells displayed an activated and mature phenotype. Moreover, compared with liver-resident NK cells and conventional NK(cNK) cells, CD49a^(+)CD49b^(+) NK cells showed increased functional competence, as evidenced by higher amounts of IFN-γ production and stronger cytotoxic capabilities during viral infection. Generation of these CD49a^(+)CD49b^(+) NK cells was shown to be independent of the T-bet transcription factor. Adoptive transfer experiments revealed that c NK cells could convert into CD49a^(+)CD49b^(+) NK cells following viral infection. Collectively, these results suggest that viral infection-induced CD49a^(+)CD49b^(+) NK cells represent a transiently activated state of cNK cells.

关键词： NK cells liver viral infection cell activation effector function

The lncRNA Snhg1-Vps13D vesicle trafficking system modulates the dual effects of IL-7 signaling to control memory CD8 T cell establishment

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The lncRNA Snhg1-Vps13D vesicle trafficking system modulates...

Yin and Yang regulation of Tfh cells

第十四届全国免疫学学术大会

作者： Yanyan Zhang Baohua Li Qiang Bai Lubin Jiang Ting Ni Lilin Ye Yuzhang Wu 中国科学院大学重庆医院陆军军医大学免疫所中国科学院上海巴斯德研究所复旦大学

The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation, suggesting their potential roles in T cell programs. However, the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified. Through CD8 T cell subsets profiling of lncRNAs, this study found a key lncRNA-Snhg1 with the conserved na?vehi-effectorlo-memoryhi expression pattern in CD8 T cells of both mice and human, that can promote memory formation while impeding effector CD8 in acute viral infection. Further, Snhg1 was found physically interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Rα membrane location specifically. With the deep mechanism probing, the Results show Snhg1-Vps13D regulated IL-7 signaling with its dual-function and dose-effect in memory CD8 generation, which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival, but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation. Moreover, we performed further study with finding the similar high-low-high expression pattern of human SNHG1/VPS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients. The central role of Snhg1-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potencial target for improving the vaccination effects to control the ongoing pandemic.

关键词： memory CD8 T cell lncRNA Snhg1 Vps13D IL-7R TCF-1 viral infection STAT3 Blimp1

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Yin and Yang regulation of Tfh cells

The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

第十二届全国免疫学学术大会

作者： Wu Yuzhang Xu Lifan ye lilin Zhou Xinyuan Third Military Medical University

Induction of the transcriptional repressor Bcl-6 in CD4+T cells is critical for the differentiation of follicular helper T cells(Tfh cells),which are essential for B cell-mediated immunity.In contrast,the transcription factor Blimpl(encoded by Prdml)inhibits Tfh differentiation by antagonizing Bcl-6.Here we found that the transcription factor TCF-1 was essential for both the initiation of Tfh differentiation and the effector function of differentiated Tfh cells

关键词： immune regulation GC reaction TCF-1 mTORC2 follicular regulatory T（Tfr） cells

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1292-1301页

作者： Leiqiong Gao Jing Zhou Sen Yang Lisha Wang Xiangyu Chen Yang Yang Ren Li Zhiwei Pan Jing Zhao Zhirong Li Qizhao Huang Jianfang Tang Li Hu Pinghuang Liu Guozhong Zhang Yaokai Chen Lilin Ye Institute of Immunology Third Military Medical UniversityChongqingChina Chongqing Public Health Medical Center ChongqingChina State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbinHeilongjiangChina College of Veterinary Medicine Northeast Agricultural UniversityHarbinHeilongjiangChina Key Laboratory of Animal Epidemiology of the Ministry of Agriculture College of Veterinary MedicineChina Agricultural UniversityBeijingChina Cancer Center The General Hospital of Western Theater CommandChengduSichuanChina Comparative Immunology Research Center College of Veterinary MedicineChina Agricultural UniversityBeijingChina

The adaptive immunity that protects patients from coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is not well characterized.In particular,the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses,but the underlying mechanisms remain unknown;meanwhile,the protective immunity that guide the recovery of these asymptomatic patients is elusive.Here,we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity(mild,n=10,moderate,n=32,severe,n=12)and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center(GC)B cell responses that result in robust and prolonged humoral immunity,assessed by GC response indicators including follicular helper T(TFH)cell and memory B cell responses as well as serum CXCL13 levels.Alternatively,these patients mounted potent virus-specific TH1 and CD8+T cell responses.In sharp contrast,patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses;however,the virus-specific TH1 and CD8+T cells were minimally induced in these patients.These results,therefore,uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity,providing important insights into rational design of effective COVID-19 vaccines.

关键词： immunity patients severity

A novel linear and broadly neutralizing peptide in the SARS-CoV-2 S2 protein for universal vaccine development

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Cellular & Molecular Immunology 2021年第11期18卷 2563-2565页

作者： Tuofan Li Qiuqi Kan Jinying Ge Zhimin Wan Mengqi Yuan Yao Huang Quan Xie Yi Yang Hongxia Shao Xiangdong Li Lilin Ye Aijian Qin Zhigao Bu Pinghuang Liu Jianqiang ye Jiangsu Coinnovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou UniversityYangzhou225009JiangsuChina Key Laboratory of Jiangsu Preventive Veterinary Medicine Key Laboratory for Avian Preventive MedicineMinistry of EducationCollege of Veterinary MedicineYangzhou UniversityYangzhou225009JiangsuChina Joint International Research Laboratory of Agriculture and Agri-Product Safety the Ministry of Education of ChinaYangzhou UniversityYangzhou225009JiangsuChina Institutes of Agricultural Science and Technology Development Yangzhou UniversityYangzhou225009JiangsuChina State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural Sciences150069HarbinChina National High Containment Laboratory for Animal Diseases Control and Prevention 150069HarbinChina College of Veterinary Medicine China Agricultural University100193BeijingChina Center of Diseases Control and Prevention Yangzhou225009JiangsuChina Institute of Immunology PLAThird Military Medical University400038ChongqingChina

As humans continue to develop COVID-19 widely,numerous novel variants of SARS-CoV-2 have emerged[1,2].These variants,which may possess enhanced transmissibility and often result in breakthrough infections in the vaccinated population,pose great challenges to the current vaccine strategies targeting the immunodominance of the receptor-binding domain(RBD)of the spike(S)protein[2].

关键词： vaccine neutral breakthrough

慢性病毒感染CD8 T细胞免疫应答及相关治疗性疫苗研究

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中国基础科学 2017年第3期19卷 7-11+19页

作者：叶丽林第三军医大学

持续性慢性病毒感染是公共健康的重大威胁。慢性病毒感染通常造成CD8 T细胞功能耗竭,而不能清除病毒感染。目前尚缺乏能有效地降低病毒滴度,延缓疾病的进程化学药物。本项目通过采用HIV感染病人样本及慢性病毒感染小鼠动物模型,发现了... 详细信息

持续性慢性病毒感染是公共健康的重大威胁。慢性病毒感染通常造成CD8 T细胞功能耗竭,而不能清除病毒感染。目前尚缺乏能有效地降低病毒滴度,延缓疾病的进程化学药物。本项目通过采用HIV感染病人样本及慢性病毒感染小鼠动物模型,发现了抗慢性病毒感染的关键CD8 T细胞亚群,这群细胞亚类可以作为免疫细胞治疗的一种新的靶标,其过继转移后,可以高效地清除病毒;并且,该群细胞的过继转移治疗还可与PD-L1抗体协同作用,更好的发挥抗病毒感染的作用。同时,在项目研究期间,我们还创立了一种以CD4 T细胞表位为基础的异源性初始-加强免疫策略,作为治疗性疫苗能高效治疗慢性病毒感染。这两项突破性研究进展为将来采用免疫学策略来"功能性治愈"HIV及其他慢性病毒感染奠定理论基础及提供技术储备。

关键词：慢性病毒感染 CD8~+ T细胞耗竭 CX-CR5~+CD8~+ T细胞 CD4~+ T细胞表位初始-加强免疫策略治疗性疫苗免疫治疗