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| 1 | CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma显示文摘SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a'spike protein-CD147-CyPA signaling axis':Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment. | Jiejie Geng Liang Chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo Chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun Chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu Zhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 6 |
| 2 | Immunological and metabolic characteristics of the Omicron variants infection显示文摘The Omicron variants of SARS-CoV-2,primarily authenticated in November 2021 in South Africa,has initiated the 5th wave of global pandemics.Here,we systemically examined immunological and metabolic characteristics of Omicron variants infection.We found Omicron resisted to neutralizing antibody targeting receptor binding domain(RBD)of wildtype SARS-CoV-2.Omicron could hardly be neutralized by sera of Corona Virus Disease 2019(COVID-19)convalescents infected with the Delta variant.Through mass spectrometry on MHC-bound peptidomes,we found that the spike protein of the Omicron variants could generate additional CD8+T cell epitopes,compared with Delta.These epitopes could induce robust CD8+T cell responses.Moreover,we found booster vaccination increased the cross-memory CD8+T cell responses against Omicron.Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells.Consistently,a greater fraction of memory CD8+T cells existed in Omicron stimulated peripheral blood mononuclear cells(PBMCs).In addition,CD147 was also a receptor for the Omicron variants,and CD147 antibody inhibited infection of Omicron.CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia.Taken together,our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron. | Jiejie Geng Xu Yang Kun Wang Ke Wang Ruo Chen Zhi-Nan Chen Chuan Qin Guizhen Wu Youchun Wang Ke Xu Peng Du Jiangning Liu Shirui Chen Tao Zhang Xiuxuan Sun Ting Guo Ying Shi Zheng Zhang Ding Wei Peng Lin Qingyi Wang Jing Yuan Jiuxin Qu Jin Zou Yingxia Liu Hongzhou Lu Ping Zhu Huijie Bian Liang Chen | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 0 |
| 3 | CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis显示文摘Regulatory T cell(Treg)stability is necessary for the proper control of immune activity and tissue homeostasis.However,it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological conditions.Foxp3 has been characterized as a central mediator of the genetic program that governs Treg stability.Here,we demonstrate that to maintain Foxp3 protein expression,Tregs require cell-to-cell contact,which is mediated by the CD147-CD98 interaction.As Tregs are produced,CD147,which is expressed on their surface,is stimulated by CD98,which is widely expressed in the physiological environment.As a result,CD147’s intracellular domain binds to CDK2 and retains it near the membrane,leading to Foxp3 dephosphorylation and the prevention of Foxp3 degradation.In addition,the optimal distribution of Foxp3+Tregs under both pathological and physiological conditions depends on CD98 expression.Thus,our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding environment.More importantly,Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability,which has guiding significance for the application of Tregs in immunotherapy. | JieJie Geng Ruo Chen Feng-fan Yang Peng Lin Yu-meng Zhu Xianghui Fu Ke Wang Zhuan Feng Jiao Wu Hai Zhang Qi-jing Li Zhi-Nan Chen Ping Zhu | 2021 | Cellular & Molecular Immunology2021，18，12： | 0 |
| 4 | CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis显示文摘COVID‐19 patients can develop clinical and histopathological features associated with fibrosis,but the pathogenesis of fibrosis remains poorly understood.CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants,which could initiate COVID-19-related cytokine storm.Here,we systemically analyzed lung pathogenesis in SARS-CoV-2-and its delta variant-infected humanized CD147 transgenic mice.Histopathology and Transmission Electron Microscopy revealed inflammation,fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs.Consistently,RNA-sequencing identified a set of fibrosis signature genes.Furthermore,we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2.We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts,decreasing susceptibility to bleomycin-induced pulmonary fibrosis.Meplazumab,a CD147 antibody,was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins,thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2.In conclusion,we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis. | Jiao Wu Liang Chen Chuan Qin Fei Huo Xue Liang Xu Yang Kui Zhang Peng Lin Jiangning Liu Zhuan Feng Jiansheng Zhou Zhuo Pei Yatao Wang Xiu-Xuan Sun Ke Wang Jiejie Geng Zhaohui Zheng Xianghui Fu Man Liu Qingyi Wang Zheng Zhang Huijie Bian Ping Zhu Zhi-Nan Chen | 2022 | Signal Transduction and Targeted Therapy2022，7，12： | 0 |
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