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| 1 | Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies显示文摘Coronavirus disease 2019(COVID-19),caused by the novel human coronavirus SARS-CoV-2,is currently a major threat to public health worldwide.The viral spike protein binds the host receptor angiotensin-converting enzyme 2(ACE2)via the receptor-binding domain(RBD),and thus is believed to be a major target to block viral entry.Both SARS-CoV-2 and SARS-CoV share this mechanism.Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies.The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice;however,the cross-neutralizing activity was much weaker,indicating that there are distinct antigenic features in the RBDs of the two viruses.This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2.It is worth noting that a newly developed SARS-CoV-2 human antibody,HA001,was able to neutralize SARS-CoV-2,but failed to recognize SARS-CoV.Moreover,the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD,representing new binding sites for neutralizing antibodies.Overall,our study has revealed the presence of different key epitopes between SARS-CoV and SARSCoV-2,which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable. | Chunyan Yi Xiaoyu Sun Jing Ye Longfei Ding Meiqin Liu Zhuo Yang Xiao Lu Yaguang Zhang Liyang Ma Wangpeng Gu Aidong Qu Jianqing Xu Zhengli Shi Zhiyang Ling Bing Sun | 2020 | Cellular & Molecular Immunology2020，17，6： | 13 |
| 2 | Development of retinol-binding protein 4 immunocolloidal gold fast test strip using high-sensitivity monoclonal antibodies generated by DNA immunization显示文摘DNA 免疫是为高亲密关系的 monoclonal 抗体产生的一个有效方法。这里,我们对松香油绑定蛋白质 4 描述几高质量的 monoclonal 抗体(mAbs ) 的产生(RBP4 ) ,为肾反常和机能障碍的一个重要标记,与 DNA 的一个联合方法, priming 和蛋白质增加。产生的 mAbs 能与高敏感并且用这些 mAbs 绑在 RBP4,一块 immunocolloidal 金牌快测试长带被构造。长带能交上结果 < 5 min 并且与大约 1 ng/ml 的察觉限制是很敏感的。小规模的临床的测试表明这脱衣的结果根据在市场上当前可得到的一个标记酶的 immunosorbent 试金工具包的好。因而,它能为在诊所的更方便、更快的 RBP4 决心是有用的。 | Chao Bian Fang Zhang Feng Wang Zhiyang Ling Min Luo Hongqiang Wu Yizhuo Sun Junhui Li B ingnan Li Jingyan Zhu Linna Tang Yanyan Zhou Qunfang Shi Yongyong Ji Lin Tian Guomei Lin Yu Fan Niansong Wang Bing Sun | 2010 | Acta Biochimica et Biophysica Sinica2010，42，12： | 2 |
| 3 | Protective humoral immunity in SARS-CoV-2 infected pediatric patients显示文摘After the rapid spread of SARS-CoV-2 in Wuhan,China,at the beginning of 2020,about 1.5 million confirmed cases and over 80,000 deaths have been reported around 200 countries and territories all over the world and the number continues to increase.However,we still have limited knowledge of this new coronavirus,especially the interaction between SARS-CoV-2 and our immune system. | Yaguang Zhang Jin Xu Ran Jia Chunyan Yi Wangpeng Gu Pengcheng Liu Xinran Dong Hao Zhou Bo Shang Shipeng Cheng Xiaoyu Sun Jing Ye Xuezhen Li Jia Zhang Zhiyang Ling Liyan Ma Bingbing Wu Mei Zeng Wenhao Zhou Bing Sun | 2020 | Cellular & Molecular Immunology2020，17，7： | 2 |
| 4 | Lactate anions participate in T cell cytokine production and function显示文摘After antigen stimulation, T cells preferentially increase aerobic glycolysis to meet the bioenergetic and biosynthetic demands of T cell activation, proliferation, and effector functions. Lactate, a by-product of glycolysis, has been reported to function as an important energy source and signaling molecule. Here, we found that lactate anions are involved in cytokine production in Tcells after TCR activation. During ex vivo T cell activation, the addition of excess sodium lactate(Na L) increased the production of cytokines(such as IFNγ/IL-2/TNFα) more than the addition of sodium chloride(NaCl). This enhanced cytokine production was dependent on TCR/CD3 activation but not CD28 activation. In vivo, Na L treatment inhibited tumour growth in subcutaneously transplanted tumour models in a T cell-dependent manner, which was consistent with increased T cell cytokine production in the Na L treatment group compared to the Na Cl treatment group. Furthermore, a mechanistic experiment showed that this enhanced cytokine production was regulated by GAPDH-mediated post-transcriptional regulation. Taken together, our findings indicate a new regulatory mechanism involved in glycolysis that promotes T cell function. | Jing Wen Shipeng Cheng Yaguang Zhang Ran Wang Jiefang Xu Zhiyang Ling Liyan Ma Xinghao Ai Bing Sun | 2021 | Science China(Life Sciences)2021，64，11： | 2 |
| 5 | HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation显示文摘Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s. | Zhishuo Wang Chenghua Yan Qizhen Du Yuying Huang Xuezhen Li Dan Zeng Ruizhi Mao Rama Krishna Gurram Shipeng Cheng Wangpeng Gu Lin Zhu Weiguo Fan Liyan Ma Zhiyang Ling Ju Qiu Dangsheng Li Enmei Liu Yaguang Zhang Yiru Fang Jinfang Zhu Bing Sun | 2023 | Cellular & Molecular Immunology2023，20，4： | 1 |
| 6 | Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation显示文摘Interleukin-33(IL-33)is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis.The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation,but the mechanism is still unclear.Here,we found that healthy individuals had higher phosphate-pyridoxal(PLP,an active form of vitamin B6)concentrations in the serum than asthma patients.Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation.In a mouse model of lung inflammation,we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33.A mechanistic study showed that in vivo,pyridoxal(PL)needed to be converted into PLP,which inhibited the type 2 response by regulating IL-33 stability.In mice heterozygous for pyridoxal kinase(PDXK),the conversion of PL to PLP was limited,and IL-33 levels were increased in the lungs,aggravating type 2 inflammation.Furthermore,we found that the mouse double minute 2 homolog(MDM2)protein,an E3 ubiquitin-protein ligase,could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells.PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway.In addition,inhalation of PLP alleviated asthma-related effects in mouse models.In summary,our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response,which might help develop a potential preventive and therapeutic agent for allergy-related diseases. | Songling Zhu Shufen Zhong Kebin Cheng Li-Sha Zhang Jiu-wu Bai Zu Cao Su Wang Wen Chen Shipeng Cheng Liyan Ma Zhiyang Ling Yuying Huang Wangpeng Gu Xiaoyu Sun Chunyan Yi Meng Zhao Shuo Liang Jin-Fu Xu Bing Sun Yaguang Zhang | 2023 | Cellular & Molecular Immunology2023，20，7： | 1 |
| 7 | Transformation of 14C-pyrimidynyloxybenzoic herbicide ZJ0273 in aerobic soils显示文摘 | WANG Haiyan YU Zhiyang YU Ling | 2010 | Science of the Total Environment2010，408，10： | 1 |
| 8 | Transformation of 14C-pyrimidinyloxybenzoic herbicide ZJ0273 in aerobic soils 显示文摘 | WANG Haiyan YU Zhiyang YUE Ling | 2010 | Sci Total Environ2010，408，10： | 1 |
| 9 | A SARS-CoV-2 antibody retains potent neutralization against Omicron by targeting conserved RBM residues显示文摘The newly emerged Omicron(B.1.1.529)variant of SARS-CoV-2 is quickly overtaking the Delta variant and becoming the dominant strain around the world due to its enhanced transmissibility and high immune escape potential[1,2].Compared to the Wuhan strain,the Omicron variant carries 37 spike mutations,of which 15 are within the receptor-binding domain(RBD)(Fig.1A).A high mutation rate is associated with remarkable resistance to current vaccines and RBD-specific antibody therapeutics[2,3,4]. | Chunyan Yi Zhiyang Ling Xiao Lu Yadong Fu Zhuo Yang Sonam Wangmo Shuangfeng Chen Yaguang Zhang Liyan Ma Wangpeng Gu Hongzhou Lu Xiaoyu Sun Bing Sun | 2022 | Cellular & Molecular Immunology2022，19，5： | 1 |
| 10 | Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody显示文摘Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is essential in this endeavor.We generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.This antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2.We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization.We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6.This motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding model.Next,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization activity.Interestingly,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs.Overall,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains. | Chunyan Yi Jing Xia Lan He Zhiyang Ling Xuesong Wang Yu Yan Jiangjun Wang Xinhao Zhao Weiguo Fan Xiaoyu Sun Ronghua Zhang Sheng Ye Rongguang Zhang Yongfen Xu Liyan Ma Yaguang Zhang Honglin Zhou Zhong Huang Junqi Niu Gang Long Junxia Lu Jin Zhong Bing Sun | 2021 | Cellular & Molecular Immunology2021，18，3： | 0 |
| 11 | Potential contribution of increased soluble IL-2R to lymphopenia in COVID-19 patients显示文摘Since the outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),more than 6 million cases are confirmed and over 300,000 cases are dead after infection.Dysfunction of immunity in COVID-19 patients has been considered as one of the fatal factors for patients,especially cytokine release syndrome and lymphopenia.1,2,3 The reduced number and increased exhaustion level of lymphocyte are associated with elevated inflammatory cytokines in COVID-19 patients.4,5 However,the mechanism of cytokine-induced lymphopenia in COVID-19 is very unclear.IL-2 is critical for the proliferation,differentiation,and function of T cells,including Tregs,CD4+,and CD8+effector cells.6 Here,we reported the negative relationship between the concentration of soluble IL-2 receptor(sIL-2R)and T-cell number in blood from COVID-19 patients.In vitro addition of recombinant CD25 could inhibit the proliferation and function of T cells from PBMC after stimulated with TCR signaling,which could be rescued by strong IL-2 signaling.Our data suggested the importance of IL-2 signaling in lymphopenia of COVID-19 patients. | Yaguang Zhang Xiaojing Wang Xuezhen Li Dong Xi Ruizhi Mao Xiaohui Wu Shipeng Cheng Xiaoyu Sun Chunyan Yi Zhiyang Ling Liyan Ma Qin Ning Yiru Fang Bing Sun Di Wu | 2020 | Cellular & Molecular Immunology2020，17，8： | 0 |
| 12 | Broad strategies for neutralizing SARS-CoV-2 and other human coronaviruses with monoclonal antibodies显示文摘Antibody therapeutics and vaccines for coronavirus disease 2019(COVID-19)have been approved in many countries,with most being developed based on the original strain of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 has an exceptional ability to mutate under the pressure of host immunity,especially the immune-dominant spike protein of the virus,which is the target of both antibody drugs and vaccines.Given the continuous evolution of the virus and the identification of critical mutation sites,the World Health Organization(WHO)has named 5 variants of concern(VOCs):4 are previously circulating VOCs,and 1 is currently circulating(Omicron).Due to multiple mutations in the spike protein,the recently emerged Omicron and descendent lineages have been shown to have the strongest ability to evade the neutralizing antibody(NAb)effects of current antibody drugs and vaccines.The development and characterization of broadly neutralizing antibodies(bNAbs)will provide broad strategies for the control of the sophisticated virus SARS-CoV-2.In this review,we describe how the virus evolves to escape NAbs and the potential neutralization mechanisms that associated with bNAbs.We also summarize progress in the development of bNAbs against SARS-CoV-2,human coronaviruses(CoVs)and other emerging pathogens and highlight their scientific and clinical significance. | Zhiyang Ling Chunyan Yi Xiaoyu Sun Zhuo Yang Bing Sun | 2023 | Science China(Life Sciences)2023，66，4： | 0 |
| 13 | A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F显示文摘Respiratory syncytial virus(RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion(F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies(hm Abs) against prefusion F protein(pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hm Ab, named as 25-20, is selected, which targets a new site Φ-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline(i GL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection. | Chunyan Yi Caixia Su Xiaoyu Sun Xiao Lu Chuanya Si Caixuan Liu Zhuo Yang Hong Yuan Yuying Huang Jing Wen Yonghui He Yaguang Zhang Liyan Ma Yao Cong Gan Zhao Zhiyang Ling Bin Wang Bing Sun | 2023 | Science China(Life Sciences)2023，66，4： | 0 |
| 14 | TRIM34 attenuates colon inflammation and tumorigenesis by sustaining barrier integrity显示文摘Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify a novel function of TRIM34 in goblet cells(GCs)in controlling inner mucus layer generation.Upon DSS treatment,TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer.This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer.Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis,thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands.Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis(UC)and the prognosis of rectal adenocarcinoma.This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis. | Qiaoshi Lian Shanshan Yan Qi Yin Chenghua Yan Wanwei Zheng Wangpeng Gu Xinhao Zhao Weiguo Fan Xuezhen Li Liyan Ma Zhiyang Ling Yaguang Zhang Jie Liu Jinsong Li Bing Sun | 2021 | Cellular & Molecular Immunology2021，18，2： | 0 |
| 15 | Jigsaw puzzle of SARS-CoV-2 RBD evolution and immune escape显示文摘The outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes coronavirus disease 2019(COVID-19),has posed a tremendous threat to global health,resulting in over 510 million infections and at least 6.23 million deaths worldwide as of early May 2022.Extensive efforts to fight against the SARS-CoV-2 pandemic have accelerated the research and clinical development of various vaccines and neutralizing antibodies(NAbs)[1,2].However,SARS-CoV-2 has an exceptional ability to mutate and evade the human immune system,which highlights the surveillance of SARS-CoV-2 evolution to anticipate and facilitate a timely response to new variants that could impact viral transmissibility and the efficacy of vaccines and antibody therapies[3]. | Chunyan Yi Xiaoyu Sun Zhiyang Ling Bing Sun | 2022 | Cellular & Molecular Immunology2022，19，7： | 0 |
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