HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-15 DOI:10.1159/000538749

Yujuan Ren, Qianqian Ying, Ying Chen, Cong Liao, Anrong Li, Qidong Ye

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Abstract

Introduction: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development.

Methods: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry.

Results: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb.

Conclusion: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

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通过促进 MHC-II 介导的抗原呈递，HLA-DRB5 的过表达可促进免疫性血小板减少症小鼠模型中血小板的减少。

导言：主要组织相容性复合体II（MHC-II）介导的抗原呈递是免疫性血小板减少症（ITP）的发病机制之一。人类白细胞抗原（HLA）-DRB5是一种MHC-II分子，本研究旨在探讨其在ITP发病中的作用和机制：方法：豚鼠抗小鼠血小板（PLT）血清诱导的ITP小鼠尾静脉注射HLA-DRB5过表达腺病毒载体/髓系细胞上表达的免疫受体-1（IREM-1）单克隆抗体（mAb）。小鼠血液中的 PLT 计数变化由血液分析仪进行评估。小鼠血液中 MHC-II/CD80/CD86 的表达通过实时定量 PCR 和免疫荧光检测进行测量。流式细胞术检测小鼠血液中 CD8+ T 细胞的比例：结果：HLA-DRB5过表达加剧了ITP小鼠模型建立第5天起PLT的减少，并增强了ITP小鼠血液中MHC-II/CD80/CD86表达的上调和CD8+ T细胞比例的升高，而IREM-1 mAb可逆转其影响：结论：HLA-DRB5过表达可上调MHC-II介导的CD8+ T细胞抗原呈递，从而降低ITP小鼠模型的PLT计数。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.