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Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells

Genes & Diseases 2021年第3期8卷 344-352页

作者： Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S.Westerberg Chaohong Liu Department of Pathogen Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China Department of Immunology School of MedicineYangtze UniversityJingzhouHubei Province434023PR China Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430030PR China The second Department of Pediatrics Affiliated Hospital of Zunyi Medical UniversityZunyiGuiZhou Province563000PR China Department of Microbiology Tumor and Cell Biology Karolinska InstitutetStockholm17177Sweden

Ubiquitin-specific peptidase 18(UsP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory T(Treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of UsP18 on the impact of Treg cell differentiation and function.We found that UsP18 deficiency upregulates the differentiation of Treg cells,which may lead to disrupted homeostasis of peripheral T cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)T cells and INF-γproducing CD8^(+)T cells.Mechanistically,we also found that the upre-gulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO Tregs is downregulated.Altogether,our study was the first to identify the role of UsP18 in Tregs differentiation and its suppressive function,which may provide a new reference for the treatment of Treg function in many autoimmune diseases,and UsP18 can be used as a new therapeutic target for precise medical treatment.

关键词： CD25 Foxp3 ICOs Regulator T cell UsP18

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sARs-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

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signal Transduction and Targeted Therapy 2021年第10期6卷 3119-3131页

作者： Yukai Jing Li Luo Ying Chen Lisa S.Westerberg Peng Zhou Zhiping Xu Andres A.Herrada Chan-sik Park Masato Kubo Heng Mei Yu Hu Pamela Pui-Wah Lee Bing Zheng Zhiwei sui Wei Xiao Quan Gong Zhongxin Lu Chaohong Liu Department of Medical Laboratory The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople's Republic of China Department of Emergency Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanPeople's Republic of China Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople's Republic of China Department of Pathogen Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople's Republic of China Center for Biosafety Mega science Wuhan Institute of VirologyChinese Academy of SciencesWuhanPeople's Republic of China Department of Microbiology Tumor and Cell Biology Karolinska InstituteStockholmSweden Wuhan Metware Biotechnology Co. LtdWuhanPeople's Republic of China Lymphatic and Inflammation Research Laboratory Facultad de Ciencias de la SaludInstituto de Ciencias BiomOdicasUniversidad Autdnoma de ChileTalcaChile Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Laboratory for Cytokine Regulation Center for Integrative Medical Science(IMS)RIKEN Yokohama InstituteKanagawaJapan Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople's Republic of China Department of Paediatrics and Adolescent Medicine LKS Faculty of MedicineThe University of Hong KongHong KongPeople's Republic of China Department of Immunology School of MedicineYangtze UniversityJingzhouHubei ProvincePeople's Republic of China Clinical Molecular Immunology Center School of MedicineYangtze UniversityJingzhouHubei ProvincePeople's Republic of China Center for Advanced Measurement science National Institute of MetrologyBeijingPeople's Republic of China Department of Respiratory The First Affiliated Hospital of Yangtze UniversityJingzhouHubei ProvincePeople's Republic of China

The sARs-CoV-2 infection causes severe immune disruption.However,it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients.In our study,we have characterized the immunephe no type of B cells from 15 recovered COVID-19 patients,and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation,but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation.However,the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation.Interestingly,we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients.Moreover,the BCR signaling and early B-cell response were disrupted upon BCR stimulation.Mechanistically,we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism.In conclusion,we found that sARs-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhandng B-cell metabolism,which may provide a new intervention target to cure COVID-19.

关键词： patients metabolism CD19

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正压呼吸治疗多种严重疾病患儿的疗效

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世界核心医学期刊文摘（儿科学分册） 2005年第9期1卷 53-53页

作者： Lagerkvist A.-L. sten G. westerberg B. 李开 Department of Physiotherapy Queen Silvia Children's Hospital SE-416 85 Gteborg Sweden

Background: Children with multiple severe disabilities cannot be spontaneously physically active and therefore lack the ventilatory stimulation of physical activity. They often produce large quantities of airway mucus, which they have difficulty to evacuate on their own. The accumulation of mucus may lead to respiratory insufficiency. Aim: To investigate whether chest physiotherapy with positive expiratory pressure (PEP)-could improve the blood oxygen tension (PO2) and/or decrease carbon dioxide tension (PCO2) in severely disabled children with airway mucus accumulation. Methods: Eighteen disabled children (mean age 7.5 y, sD 4.3, range 1.7-17.8 y) participated in the study. Transcutaneous (tc) PO2, tcPCO2 and respiratory rate (RR) were recorded before and after PEP treatment. The reproducibility of the effect of the treatment was tested by repeating the recordings. Results: The mean tcPO2 increased 1.0 kPa (range -0.2 to 3.4 kPa) immediately after PEP treatment (p=0.0001). No significant changes in tcPCO2 or RR were noted. The reproducibility of the effect of PEP treatment was good, with a significant increase in tcPO2 at all retests. All children accepted the treatment well. Conclusion: PEP increases blood oxygen tension immediately after treatment in severely disabled children with airway mucus accumulation. Long-term effects remain to be proven.

关键词：疾病患儿正压呼吸氧张力重症患儿二氧化碳张力呼吸障碍呼吸运动呼吸频率可重复性长期效果

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东非高地:不稳定坡地,不稳定环境?

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人类环境杂志 1999年第5期28卷 419-429页

作者： Lars-Ovewesterberg Carl Christiansson 高书平斯德哥尔摩大学斯德哥尔摩大学自然地理学中国地质出版社

土体滑坡遍布全球,是影响陡斜坡地的地貌过程。土体滑坡研究形形色色,但过去主要致力于温带和冰缘地区,而热带陡坡地很少涉及。本文综合了20世纪90年代初期以来在肯尼亚Nyan-darua岭和赞比亚Uluguru山开展的土体滑坡研究的成果。研究范... 详细信息

土体滑坡遍布全球,是影响陡斜坡地的地貌过程。土体滑坡研究形形色色,但过去主要致力于温带和冰缘地区,而热带陡坡地很少涉及。本文综合了20世纪90年代初期以来在肯尼亚Nyan-darua岭和赞比亚Uluguru山开展的土体滑坡研究的成果。研究范围包括土体滑坡的过程和原因、滑坡凹地恢复状况以及从长期来看对景观地貌的影响。有些观点是有争论的:土体滑坡是高原地区最常见的剥蚀营力;土体滑坡发生的必要条件在自然界是充足的,与人类活动引起的土体滑坡相比,自然条件绝对重要得多。地形表明,土体滑坡在长期的地貌景观刻蚀中是最重要的营力。滑坡凹地的恢复惊人地快。在Uluguru山,滑坡凹地在大约20年内就恢复了农业生产;在Nyandarua岭,滑坡凹地表土的物理和化学性能10年中恢复得相当好。因此,土体滑坡引起的土地退化作用具有暂时特征。

关键词：东非地区土体滑坡土体退化地形演化坡地演变

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