Effect of high mobility group box 1 on Toll-like receptor 9 in B cells in myeloperoxidase-ANCA-associated vasculitis
Effect of high mobility group box 1 on Toll-like receptor 9 in B cells in myeloperoxidase-ANCA-associated vasculitis
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高迁移率族蛋白1对髓过氧化物酶-ANCA相关性血管炎B细胞Toll样受体9的影响
DOI：
10.1080/08916934.2019.1696777
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发表时间：
2019-12
期刊：
影响因子：
3.5
通讯作者：
Zhao Ming-Hui
中科院分区：
文献类型：
--
作者：
Wang Chen;Deng Hui;Gong Yan;You Ran;Chen Min;Zhao Ming-Hui
高迁移率族蛋白1（HMGB 1）在抗神经细胞胞浆抗体（ANCA）相关性血管炎（AAV）中起致病作用。最近的研究表明，Toll样受体9（TLR 9）参与了自身免疫性疾病（包括AAV）的B细胞耐受破坏。本实验研究了HMGB 1对AAV B细胞TLR 9表达的影响。在目前的工作中，患者髓过氧化物酶（MPO）-AAV在活动期招募。采用流式细胞术检测不同B细胞亚群中细胞内TLR 9的表达，并与临床资料进行相关性分析。结果表明，B细胞、记忆B细胞和浆母细胞内TLR 9的表达与红细胞沉降率（ESR）和C反应蛋白（CRP）相关。具体而言，浆细胞中的TLR 9表达与ESR、CRP、血清肌酐、eGFR和伯明翰血管炎活动评分相关。为了进一步探讨HMGB 1对B细胞的影响，从AAV患者中分离外周血单个核细胞（PBMCs）。流式细胞仪检测HMGB 1刺激后不同B细胞亚群中TLR 9的表达及活B细胞的增殖率。我们发现，TLR 9在浆细胞中的表达和活B细胞的增殖率由HMGB 1刺激与对照组相比显著上调。因此，浆细胞中TLR 9的表达与MPO-AAV的疾病活动相关。HMGB 1可促进浆细胞TLR 9表达和B细胞增殖。提示HMGB 1对MPO-AAV介导的B细胞TLR 9表达的影响，为MPO-AAV的干预策略提供了可能的线索。
Abstract High mobility group box 1 (HMGB1) played pathogenic role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent findings demonstrated that Toll-like receptor 9 (TLR9) was involved in B cell tolerance breaking of autoimmune disease, including AAV. Here, we investigated the effect of HMGB1 on TLR9 in B cells of AAV. In the present work, patients with myeloperoxidase (MPO)-AAV in active stage were recruited. Intracellular TLR9 expression in various B cell subpopulations of the whole blood was detected by flow cytometry and the correlation with clinical data was analysed. Our results showed that intracellular TLR9 expression in B cells, memory B cells and plasmablasts correlated with erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). In particular, TLR9 expression in plasma cells correlated with ESR, CRP, serum creatinine, eGFR, and Birmingham Vasculitis Activity Score. To further explore the effect of HMGB1 on B cell, peripheral blood mononuclear cells (PBMCs) from AAV patients were isolated. After stimulated with HMGB1, TLR9 expression in various B cell subpopulations and proliferation ratio of live B cells were analysed by flow cytometry. We found that TLR9 expression in plasma cells and the proliferation ratio of live B cells by HMGB1 stimulation were significantly upregulated compared with the control group. Therefore, TLR9 expression in plasma cells was associated with disease activity of MPO-AAV. HMGB1 could enhance TLR9 expression in plasma cells and B cell proliferation. These indicated a role of HMGB1 on TLR9 in B cells in MPO-AAV, which would provide potential clues for intervention strategies.
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影响因子：
3.4
作者：
Boldt, Andreas;Borte, Stephan;Sack, Ulrich
通讯作者：
Sack, Ulrich
DOI：
10.1093/oxfordjournals.qjmed.a068882
发表时间：
1994-11
期刊：
QJM : monthly journal of the Association of Physicians
影响因子：
--
作者：
R. Luqmani;P. Bacon;R. Moots;B. A. Janssen;A. Pall;P. Emery;C. Savage;D. Adu
通讯作者：
R. Luqmani;P. Bacon;R. Moots;B. A. Janssen;A. Pall;P. Emery;C. Savage;D. Adu
影响因子：
5.4
作者：
Jiang, Wei;Lederman, Michael M.;Sieg, Scott F.
通讯作者：
Sieg, Scott F.
影响因子：
4.7
作者：
Wang, Chen;Gou, Shen-Ju;Chen, Min
通讯作者：
Chen, Min
DOI：
10.1016/b978-012455900-4/50268-3
发表时间：
2005-01-01
期刊：
MEASURING IMMUNITY: BASIC BIOLOGY AND CLINICAL ASSESSMENT
影响因子：
--
作者：
Hawn, Thomas R.;Underhill, David M.
通讯作者：
Underhill, David M.