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Abstract：
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a low platelet (PLT) count and a high risk of bleeding, the clinical treatment for which still needs to be upgraded. Based on the critical role of human leukocyte antigen class II heterodimer β5 (HLA-DRB5) in immune system, we herein investigated its effect on ITP. ITP murine models were established by the injection of guinea pig anti-mouse platelet serum (GP-APS), and the PLT of mouse peripheral blood was counted during the modeling. Quantitative real-time reverse transcription polymerase chain reaction, western blot and immunofluorescence assay was performed to quantify expressions of HLA-DRB5, major histocompatibility complex II (MHC-II) and co-stimulatory molecules (CD80, CD86). Flow cytometry was conducted to analyze the percentage of CD8+ T cells. As a result, the PLT count was decreased in mouse peripheral blood. Expressions of HLA-DRB5, MHC-II and co-stimulatory molecules, as well as the percentage of CD8+ T cells were elevated in peripheral blood of ITP mice. HLA-DRB5 knockdown mitigated ITP by increasing peripheral PLT level, downregulating expressions of MHC-II and co-stimulatory molecules and inactivating CD8+ T cells. Collectively, the downregulation of HLA-DRB5 restores the peripheral PLT count in ITP mice by reducing MHC-II-mediated antigen presentation of macrophages to inhibit the activation of CD8+ T cells.
摘要：
免疫性血小板减少症（ITP）是一种自身免疫性疾病，其特征是血小板（PLT）计数低和出血风险高。临床治疗仍需升级。基于人类白细胞抗原II类异二聚体β5（HLA-DRB5）在免疫系统中的关键作用，我们在此研究了其对ITP的影响。通过注射豚鼠抗鼠血小板血清(GP-APS)建立ITP小鼠模型,并在建模过程中计数小鼠外周血的PLT。定量实时逆转录聚合酶链反应,进行westernblot和免疫荧光分析以定量HLA-DRB5，主要组织相容性复合体II（MHC-II）和共刺激分子（CD80，CD86）的表达。进行流式细胞术以分析CD8+T细胞的百分比。因此,小鼠外周血PLT计数降低。HLA-DRB5、MHC-II和共刺激分子的表达,以及在ITP小鼠外周血中CD8+T细胞的百分比升高。HLA-DRB5敲低通过增加外周PLT水平减轻ITP，下调MHC-II和共刺激分子的表达并使CD8+T细胞失活。总的来说，HLA-DRB5的下调通过减少MHC-II介导的巨噬细胞的抗原呈递来抑制CD8+T细胞的活化,从而恢复ITP小鼠的外周PLT计数.
