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Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia.

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机构： [1]Department of Hematology, Qilu Hospital, Shandong University, Jinan, China [2]Department of Medical Oncology, Shandong Provincial Institute of Cancer Prevention and Treatment, Shandong Cancer Hospital, Shandong University, Jinan, China [3]West China School of Medicine, Sichuan University, Chengdu, China [4]Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China [5]Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [6]Department of Immunology, Shandong University School of Medicine, Jinan, China [7]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. [8]Toronto Platelet Immunobiology Group, University of Toronto, Toronto, ON, Canada [9]Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada [10]Canadian Blood Services Centre for Innovation, Toronto, ON, Canada [11]Department of Medical Oncology, Tianjin Medical University, Tianjin, China.

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关键词： Human leukocyte antigen-G immunoglobulin-like transcripts immune thrombocytopenia

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Human leukocyte antigen-G is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. Human leukocyte antigen-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulin-like transcripts. Here we observed significantly less human leukocyte antigen-G in plasma from immune thrombocytopenia patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls. Besides, human leukocyte antigen-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membrane-bound human leukocyte antigen-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant human leukocyte antigen-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. Human leukocyte antigen-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-α, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. Human leukocyte antigen-G-modulated dendritic cells from immune thrombocytopenia patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, human leukocyte antigen-G modulated cells from patients induced less platelet apoptosis. Human leukocyte antigen-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of human leukocyte antigen-G and immunoglobulin-like transcripts is involved in the pathogenesis of immune thrombocytopenia; Recombinant human leukocyte antigen-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that human leukocyte antigen-G can be a diagnostic marker and a therapeutic option for immune thrombocytopenia. Copyright © 2020, Ferrata Storti Foundation.

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出版当年[2021]版：

大类 | 1 区

医学

小类 | 2 区血液学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区血液学

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第一作者机构： [1]Department of Hematology, Qilu Hospital, Shandong University, Jinan, China

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通讯机构： [5]Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [11]Department of Medical Oncology, Tianjin Medical University, Tianjin, China.

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Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia.

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