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Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm

Cellular & Molecular Immunology 2021年第5期18卷 1305-1307页

作者： Jinghe Zhang Haibo Wu XiaoHong Yao Dingyu Zhang Yonggang Zhou Binqing Fu wei Wang Heng Li Zhe Wang Ziming Hu Yong Ren Rui Sun Zhigang Tian Xiuwu Bian haiming wei Department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Science and Medical CenterUniversity of Science and Technology of ChinaHefeiAnhuiChina Intelligent Pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina Institute of Pathology Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Wuhan Jinyintan Hospital(Wuhan Hospital for Infectious Diseases) WuhanHubeiChina General Hospital of Central Theater Command PLAWuhanChina

Coronavirus disease 2019(COVID-19)is an unprecedented pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).As of 22 February 2021,the worldwide pandemic has resulted in more than 110 million cases and 2.4 million deaths.1 Clinical investigation of COVID-19 patients has shown that a systemic cytokine storm can occur,especially in severe cases.2 Treatment of the SARS-CoV-2-associated cytokine storm with tocilizumab3 or anakinra4 has been shown to immediately improve the clinical outcome in most severe and critical COVID-19 patients.These data highlight the systemic cytokine storm as an important exacerbating event in severe COVID-19;however,our understanding of the molecular mechanisms involved in the initiation of the SARS-CoV-2-associated cytokine storm is limited.In the present study,we uncovered a reasonable explanation for cytokine storm initiation through the analysis of 13 autopsy samples from severe COVID-19 patients.

关键词： cytokine storm acute

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Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA

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Journal of Molecular Cell Biology 2021年第10期13卷 748-759页

作者： Dongyao Wang Dong Wang Min Huang Xiaohu Zheng Yiqing Shen Binqing Fu Hong Zhao Xianxiang Chen Peng Peng Qi Zhu Yonggang Zhou Jinghe Zhang Zhigang Tian Wuxiang Guan Guiqiang Wang haiming wei Division of Life Sciences and Medicine Department of HematologyThe First Affiliated Hospital of University of Science and Technology of ChinaUniversity of Science and Technology of ChinaHefei 230001China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medicine and Medical CenterUniversity of Science and Technology of ChinaHefei 230001China Hefei National Laboratory for Physical Sciences at Microscale University of Science and Technology of ChinaHefei 230001China Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuaZhong University of Science and TechnologyWuhan 430030China Department of Infectious Diseases Peking University First HospitalBeijing 100034China Department of Tuberculosis Wuhan Pulmonary HospitalWuhan 430030China Center for Emerging Infectious Diseases Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Peking University International Hospital Beijing 100034China

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,has become a global public health crisis.Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital.How such retest-positive(RTP)patients become infected again is not known.In this study,30 RTP patients,20 convalescent patients,and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells.We found that absolute numbers of CD4^(+)T cells,CD8^(+)T cells,and natural killer cells were not substantially decreased in RTP patients,but the expression of activation markers on these cells was significantly reduced.The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients.Through transcriptome sequencing,we demonstrated that high expression of inhibitor of differentiation 1(ID1)and low expression of interferon-induced transmembrane protein 10(IFITM10)were associated with insufficient activation of immune cells and the occurrence of RTP.These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP,which may contribute to a better understanding of the mechanisms underlying RTP.

关键词： COVID-19 CD8f T cells NK cells RTP patients immune function

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多功能蛋白聚糖与子宫内膜样腺癌的相关性研究

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云南医药 2024年第3期45卷 32-34页

作者：黄伟龙李静玲韦海明广西壮族自治区人民医院/广西医学科学院妇科广西南宁530021 广西壮族自治区人民医院/广西医学科学院病理科广西南宁530021

目的研究子宫内膜样腺癌组织中多功能蛋白聚糖的表达水平,探讨其与临床病理特征及患者预后生存的相关性。方法选2016年1月-2019年1月在广西壮族自治区人民医院因子宫内膜样腺癌入院患者120例,收集临床及病理数据,对各病例多功能蛋白... 详细信息

目的研究子宫内膜样腺癌组织中多功能蛋白聚糖的表达水平,探讨其与临床病理特征及患者预后生存的相关性。方法选2016年1月-2019年1月在广西壮族自治区人民医院因子宫内膜样腺癌入院患者120例,收集临床及病理数据,对各病例多功能蛋白聚糖表达水平进行评分,采用统计学方法分析多功能蛋白聚糖与临床病理特征及患者预后生存的相关性。结果多功能蛋白聚糖表达水平与肿瘤组织学分级、分期有显著相关性;与患者总生存期呈负相关。年龄、分级、分期、多功能蛋白聚糖表达水平与患者总生存期密切相关。多因素Cox回归分析显示,多功能蛋白聚糖是子宫内膜癌患者预后的独立危险因素。结论多功能蛋白聚糖对子宫内膜样腺癌的发生、发展有一定影响,它可能是子宫内膜样腺癌潜在的预后预测指标。

关键词：多功能蛋白聚糖子宫内膜样腺癌临床病理特征预后

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Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial

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Frontiers of Medicine 2021年第3期15卷 486-494页

作者： Dongsheng Wang Binqing Fu Zhen Peng Dongliang Yang Mingfeng Han Min Li Yun Yang Tianjun Yang Liangye Sun wei Li wei Shi Xin Yao Yan Ma Fei Xu Xiaojing Wang Jun Chen Daqing Xia Yubei Sun Lin Dong Jumei Wang Xiaoyu Zhu Min Zhang Yonggang Zhou Aijun Pan Xiaowen Hu Xiaodong Mei haiming wei Xiaoling Xu Department of Pulmonary and Critical Care Medicine the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)Hefei 230001China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230027China Intensive Care Unit the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)Hefei 230001China Drug Clinical Trail Institution the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430000China Department of Respiratory Medicine the Second People’s Hospital of FuyangFuyang 236000China Department of Respiratory Medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityXiangya Lung Cancer CenterXiangya HospitalCentral South UniversityHunan Provincial Clinical Research Center for Respiratory DiseasesChangsha 410000China Lu’an People’s Hospital Affiliated to Anhui Medical University Lu’an 237005China Department of Pulmonary and Critical Care Medicine the First Affiliated Hospital of Bengbu Medical CollegeClinical Research Center for Respiratory Disease(tumor)in Anhui ProvinceBengbu 233004China Department of Respiratory Medicine Anqing Hospital Affiliated to Anhui Medical UniversityAnqing 246000China The First Affiliated Hospital of Nanjing Medical University Nanjing 210000China Department of Rheumatology and Immunology the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)Hefei 230001China Department of Oncology the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)Hefei 230001China Department of Endocrinology

Tocilizumab has been reported to attenuate the“cytokine storm”in COVID-19 patients.We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment.We conducted a randomized,controlled,open-label multicenter trial among COVID-19 patients.The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone.The cure rate,changes of oxygen saturation and interference,and inflammation biomarkers were observed.Thirty-three patients were randomized to the tocilizumab group,and 32 patients to the control group.The cure rate in the tocilizumab group was higher than that in the control group,but the difference was not statistically significant(94.12%vs.87.10%,rate difference 95%CI−7.19%–21.23%,P=0.4133).The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12(P=0.0359).In moderate disease patients with bilateral pulmonary lesions,the hypoxia ameliorated earlier after tocilizumab treatment,and less patients(1/12,8.33%)needed an increase of inhaled oxygen concentration compared with the controls(4/6,66.67%;rate difference 95%CI−99.17%to−17.50%,P=0.0217).No severe adverse events occurred.More mild temporary adverse events were recorded in tocilizumab recipients(20/34,58.82%)than the controls(4/31,12.90%).Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative.For patients with bilateral pulmonary lesions and elevated IL-6 levels,tocilizumab could be recommended to improve outcome.

关键词： tocilizumab coronavirus disease 2019(COVID-19) cytokine storm

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The Involvement of Heat Shock Proteins in Murine Liver Regeneration

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Cellular & Molecular Immunology 2007年第1期4卷 53-57页

作者： Qing Shi Zhongjun Dong haiming wei Institute of Immunology Hefei National Laboratory for Physical Sciencesat Microscale and School of Life Sciences University of Science andTechnology of China Hefei 230027 China

Partial hepatectomy （PHx） in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins （HSPs） were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration. Cellular ＆ Molecular Immunology. 2007;4（1）：53-57.

关键词： partial hepatectomy liver regeneration heat shock protein

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Trichosanthin Induced Th2 Polarization Status

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Cellular & Molecular Immunology 2006年第4期3卷 297-301页

作者： Shuying Zhao Yanyan Wang haiming wei School of Life Sciences University of Science and Technology of China Hefei 230027 Anhui China

Trichosanthin is extracted from the root tuber of Chinese medicinal herb Trichosanthes kirilowii maximowicz （Tian Hua Fen）. TCS has abortifacient, anti-tumor, anti-HIV and immunoregulatory functions. It has been proved that it could inhibit immune response and arouse a T helper 2 response in the draining lymph node. In the current study the effect of TCS on mouse splenocytes was investigated. We stimulated C57BL/6 mice with TCS both in vivo and in vitro and analyzed the change of type 1 and type 2 cytokines in mouse splenocytes. The results showed that TCS could induce the expression of IL-4, one of the major T helper 2 （Th2） cytokines, and inhibit the expression of IFN-γ, an important Thl cytokine in spleen lymphocytes both in vivo and in vitro. It is also shown the kinetics of Thl-to-Th2 transition after TCS stimulation in vivo in C57BL/6 mice. We found that type 2 cytokines, such as IL-10, TGF-β and IL-4 were increased regularly but IFN-γ, was decreased at day 3 and then increased. However the mechanism for cytokine change is not clear.

关键词： trichosanthin IL-4 IFN-γ Th

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NK cells promote fetal development through the secretion of growth-promoting factors

NK cells promote fetal development through the secretion of ...

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第十三届全国免疫学学术大会

作者： haiming wei Institute of Immunology School of Life Sciences and Medical Center The Key Laboratory of Innate Immunity and Chronic Disease Chinese Academy of Sciences University of Science and Technology of China

Natural killer cells (NK cells) are named for their spontaneous killing ability. NK cells are not only "sentinel" in host defense, but also play a key role in maintaining tissue homeostasis by secreting cytokines and chemokines. Disturbance in the number of mature NK cells impact tumor formation and growth as well as autoimmune disease. However, at present,whether it is the study of NK cell functional molecules or the regulation factors for promoting to NK cell development

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Increased Uterine NK-Derived IFN-γand TNF-αin C57BL/6J Mice during Early Gestation

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Cellular & Molecular Immunology 2006年第2期3卷 131-137页

作者： Xiaoyan WU haiming wei Jianhong Zhang Zhigang Tian Hefei National Laboratory for Physical Sciences at Microscale School of Life Sciences University of Science and Technology of China Hefei 230027 Anhui China

Natural killer （NK） cells are bone marrow-derived lymphocytes. They produce cytokines that regulate the development of acquired immunity. In view of their accumulation at the maternal-fetal interface, uterine natural killer （uNK） cells are also thought to play essential roles during pregnancy. Our results compared the differences of cytokine secretion profile by NK cells in uterine endometrium, liver, spleen and peripheral blood, and focused on the cytokines secretion by uNK cells. It was demonstrated that the expression of IFN-γ and TNF-α in uterine endometrium of pregnant mice are lower than those in liver, but they increase significantly during pregnancy. Our study showed that the number of uNK cells was increased significantly during pregnancy. They produced more IFN-γ and TNF-α than other organ-derived NK cells, and they also secreted minor amount of IL-4 and IL-5. The results indicated that the IFN-γ and TNF-α produced by uNK cells ensured a successful pregnancy progress.

关键词： uNK IFN-γ TNF-α IL-4 IL-5 pregnancy

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IL-16 induces inflammation in endometriosis through iron-mediated T cell pyroptosis

IL-16 induces inflammation in endometriosis through iron-med...

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第十四届全国免疫学学术大会

作者： Jinghe Zhang Binqing Fu haiming wei Institute of Immunology University of Science and Technology of China

Endometriosis is an inflammatory disease that frequently Results in severe pain and infertility that affects approximately 10% of women of reproductive age. In the present study, we showed that active Interleukin-16(IL-16) is an initiator of the proinflammatory cascade in endometriosis. By antibody chip screening and western blot as well as ELISA, we identified presence of large amounts of iron deposits in the ectopic endometrium. Furthermore, we found iron overload-induced caspase-3 and GSDME mediated pyroptosis is critical for the release of active IL-16 from ectopic endometrial T cells. Together, our study highlights the proinflammatory function of active IL-16 and uncovers a mechanism of active IL-16 release in endometriosis that is coupled to the initiation of endometriosis-associated inflammation.

关键词： iron overload IL-16 T cells pyroptosis

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Interferon-γ dependent cross-talk between antigenspecific CD4+ T cells and hepatocytes determines HBV induced peripheral tolerance

Interferon-γ dependent cross-talk between antigenspecific C...

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第八届全国免疫学学术大会

作者： Zhutian Zeng Rui Sun haiming wei Zhigang Tian Institute of Immunology School of Life Sciences University of Science and Technology of China

Chronic Hepatitis B(CHB)-induced unresponsiveness to peripheral vaccination is the biggest obstacle for development of therapeutic vaccine against CHB.However, the mechanisms responsible for CHB-induced peripheral tolerance are not precisely understood.By using a hydrodynamic injection-based HBV carrier mouse model, in comparison to wild-type(WT) HBV carrier mice, we found both interferon-γ deficient(GKO) and interferon-γ receptor 1 deficient(G RKO) HBV carrier mice that received peripheral HBsAg vaccination showed significantly HBsAg seroconversion, which was correlated to the retained HBsAg specific T cell clones in GKO HBV carrier mice.Further results showed the indispensable role of CD4+ T cells derived IFN-γ during the induction of peripheral tolerance.In a mixed bone marrow mouse model, only IFN-γ competent cells lost the HBsAg responsiveness, whereas IFN-γ deficient cells remained responsiveness to HBsAg.Moreover, bone marrow chimeric mice that lack IFN-γ receptor expression only on nonhematopoietic cells became HBsAg responsiveness, strongly indicating that IFN-γ responsive nonhematopoietic cells in liver meditated HBV induced peripheral tolerance.However, transfer of WT hepatic nonparenchymal cells could not establish the tolerance state in G RKO HBV carrier mice, whereas restore the IFN-γ R expression on liver parenchymal cells partially inhibit the responsiveness to peripheral HBsAg vaccination in G RKO HBV carrier mice, support a dominant role of hepatocytes in IFN-γ-mediated peripheral tolerance.In conclusion, our result demonstrated an undiscovered role of IFN-γ in HBV-induced peripheral tolerance.A cross-talk between HBsAg specific CD4+ T cells and hepatocytes through IFN-γ might be critical to maintain HBV tolerance.

关键词： HBV peripheral tolerance IFN-γ CD4+T cell

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