High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia  

作　　者：Feng-Qi Liu Qing-Yuan Qu Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang 

机构地区：[1]Peking University People’s Hospital,Peking University Institute of Hematology,Beijing 100044,China [2]Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing 100044,China [3]National Clinical Research Center for Hematologic Disease,Beijing 100044,China [4]Collaborative Innovation Centre of Hematology,Peking University,Beijing 100044,China [5]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [6]University of Chinese Academy of Sciences,Beijing 100049,China [7]Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100074,China [8]State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China

出　　处：《Science China(Life Sciences)》2024年第8期1635-1647,共13页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(82230004,81970113,82300149);the National Key Research and Development Program of China(2021YFC2500304);Capital Health Research and Development of Special(2022-1-4082);Peking University Medicine Fund for world's leading discipline or discipline cluster development(71003Y3035).

摘　　要：To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.

关 键 词：immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow 

分 类 号：R558.2[医药卫生—血液循环系统疾病]