检索结果-南通市图书馆

MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages

Cellular & Molecular Immunology 2023年第12期20卷 1413-1427页

作者： Jingjing Cao Lili Ji Yanxia Zhan Xia Shao Pengcheng Xu Boting Wu Pu Chen Luya Cheng Xibing Zhuang Yang Ou Fanli Hua Lihua Sun Feng Li Hao Chen Zhaocai Zhou Yunfeng Cheng Department of Hematology Zhongshan HospitalFudan UniversityShanghai200032China Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghai201508China Department of Transfusion Medicine Zhongshan HospitalFudan UniversityShanghai200032China Department of Laboratory Medicine Zhongshan HospitalFudan UniversityShanghai200032China Department of Hematology Zhongshan Hospital Qingpu BranchFudan UniversityShanghai201700China Department of Thoracic Surgery Zhongshan-Xuhui HospitalFudan UniversityShanghai200031China State Key Laboratory of Genetic Engineering Zhongshan HospitalSchool of Life SciencesFudan UniversityShanghai200438China Institute of Clinical Science Zhongshan HospitalFudan UniversityShanghai200032China

primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of inflammation.Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.The expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were determined.Macrophage phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying mechanisms.The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment.The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages.Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of MST4.In a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of thrombocytopenia.Downregulation of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of macrophages.Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.

关键词： primary immune thrombocytopenia Mammalian sterile-20-like kinase 4(MST4) Macrophages M1 polarization Signal transducer and activator of transcription-1(STAT1)

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A 10-year change of the diagnosis and treatment strategy of primary immune thrombocytopenia among Chinese hematologists

A 10-year change of the diagnosis and treatment strategy of ...

引用

第十三届全国免疫学学术大会

作者： Honghui Wang Zeping Zhou Second Affiliated Hospital of Kunming Medical University

Background: primary immune thrombocytopenia(ITP) is a disease lacked of specific diagnostic indicators. Treatments of ITP depends on the experience of physicians and the willingness of patients. AIM To investigate the change of the diagnosis and treatment of ITP among Chinese hematologists and guide the diagnosis and treatment of ITP.Methods: Questionnaires were designed to investigate the diagnosis and treatment strategy of ITP and distributed to respondents on site. Data returned after completion and analyzed by SPSS 18.0.Results: A total of 241 questionnaires was available for analysis in 2009 and 70 questionnaires were available in 2018. More than 70% hematologists selected peripheral blood smears and more than 90% doctors selected bone marrow puncture when patients were suspected of ITP. More doctors selected additional laboratory examinations to diagnose ITP ten years later(P<0.05). Most respondents thought the diagnosis of refractory ITP was not based on ineffective splenectomy(76.8% in 2009 and 73.0% in 2018). "Bleeding degree" was considered as the most important goal for ITP treatment by 42.1% hematologists in 2009 and by 68.3% hematologists in 2018(P=0.006). In 2018, criteria of starting treatment and hospitalization became more stringent(P<0.05). Using glucocorticoid with a small dose in a long period was selected as the first therapy for ITP. When platelets counts rised to 100 x 109/L, some physicians(49.6% in 2009 and 44.8% in 2018) were able to stop drug therapy. "The unforeseen effect of splenectomy" was the most influential factor for splenectomy selection(33.2% in 2009 and 41.1% in 2018).Conclution: Though Chinese hematologists have made some progress in the diagnosis and treatment of ITP these years, there still exists some differences and deficiencies compared with international guidelines. Further training and new guidelines are needed to develop and improve the skills of diagnosis and treatment of ITP in China.

关键词： primary immune thrombocytopenia change diagnosis treatment strategy Chinese hematologists

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Levels of soluble CD30 and CD26 and their clinical significance in patients with primary immune thrombocytopenia

Levels of soluble CD30 and CD26 and their clinical significa...

引用

第十三届全国免疫学学术大会

作者： Xueping Gu Honghui Wang Huiyuan Li Lingmei Yin Wei Tao Jingxing Yu Hongli Mu Jue Shen Jin Yao Lin Liu Renchi Yang Hui Bi Zeping Zhou Second Affiliated Hospital of Kunming Medical University Institute of Hematology & Blood Diseases Hospital State Key Laboratory of Experimental Hematology

Background: It has been revealed sCD30 and sCD26 were correlated with some autoimmune diseases, especially in evaluating the activity of disease. However, little research has been done on primary immune thrombocytopenia(ITP) in this area.Objectives: Our study aimed to investigate the association between sCD30 or sCD26 and ITP, and evaluate their value in ITP.Methods: This study enrolled 47 patients with ITP and 20 healthy persons. The mRNA expression of CD30 was quantified by RT-PCR. Concentrations of sCD30 and sCD26 were measured by ELISA.Results: The concentration of sCD30 was higher in active ITP patients(median, 35.82 ng/ml) than in patients in remission(median, 23.12 ng/ml;P=0.021) and healthy controls(median, 25.11 ng/ml;P=0.002). Plasma sCD26 levels were decreased in patients in remission compared with controls(median, 599.4 ng/ml vs. 964.23 ng/ml;P=0.004). No difference was found in sCD26 levels between active ITP patients and controls(P=0.072) as well as between patients in remission and active ITP patients(P=0.237). Ratios of sCD26/sCD30 in active ITP patients were decreased compared with controls(P=0.005), while no difference between ITP patients in remission and controls as well as active ITP patients(P=0.198, 0.093, respectively). By analyzing the relevance of sCD30, sCD26 and sCD26/sCD30 ratio to platelet counts, disease courses and bleeding in active ITP patients, no other relation was found except concentrations of sCD30 were positively correlated with hemorrhage(r=0.493, P=0.017).Conclusion: Levels of sCD30 and sCD26/sCD30 ratios may contribute to diagnose of ITP and evaluate the activity of disease while sCD26 could not.

关键词： primary immune thrombocytopenia sCD30 sCD26

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Advances in immunopathogenesis of adult immune thrombocytopenia

引用

Frontiers of Medicine 2013年第4期7卷 418-424页

作者： Xinguang Liu Yu Hou Jun Peng Department of Hematology Qilu HospitalShandong UniversityJinan 250012China Shandong University School of Medicine Jinan250012China

primary immune thrombocytopenia(ITP)is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production.Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP,several abnormalities involving the cellular mechanisms of immune modulation have been identified,and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction.This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia B lymphocytes T lymphocytes antigen-presenting cells cytokines

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：