Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11c+ B Cells Induced by TLR9 in Lupus.

IF 4.3 4区 医学 Q2 IMMUNOLOGY Immune Network Pub Date : 2024-06-19 eCollection Date: 2024-08-01 DOI:10.4110/in.2024.24.e25
Sung Hoon Jang, Joo Sung Shim, Jieun Kim, Eun Gyeol Shin, Jong Hwi Yoon, Lucy Eunju Lee, Ho-Keun Kwon, Jason Jungsik Song
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Abstract

Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c+ B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11chi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c+ B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11chi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c+ B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.

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线粒体活性和 CXCR4 协同促进红斑狼疮中由 TLR9 诱导的 CD11c+ B 细胞的分化
红斑狼疮的特征是针对核Ags的自身抗体,这就强调了识别驱动自身免疫的B细胞亚群的重要性。我们的研究重点是红斑狼疮患者的 CD11c+ B 细胞在体内外受到 TLR9 激动剂 CpG-寡脱氧核苷酸(ODN)刺激后的线粒体活性和 CXCR4 表达。我们还评估了注射 ODN 的小鼠 CD11c+ B 细胞的反应。在体外 ODN 刺激后,我们观察到 CD11chi 细胞比例增加,狼疮患者 CD11c+ B 细胞的线粒体活性和 CXCR4 表达升高。体内实验显示了类似的模式,TLR9刺激增强了CD11chi B细胞的线粒体和CXCR4活性,导致抗dsDNA浆细胞的产生。CXCR4 抑制剂 AMD3100 和线粒体复合体 I 抑制剂 IM156 能显著降低 CD11c+ B 细胞和自反应性浆细胞的比例。这些结果强调了线粒体和 CXCR4 在产生自反应性浆细胞中的关键作用。
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来源期刊
Immune Network
Immune Network Immunology and Microbiology-Immunology
CiteScore
2.90
自引率
3.30%
发文量
36
期刊介绍: Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity
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