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多发性硬化症中小胶质细胞结节的分析揭示了其形成病变的倾向。

Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation.

机构信息

Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.

Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands.

出版信息

Nat Commun. 2024 Feb 23;15(1):1667. doi: 10.1038/s41467-024-46068-3.

DOI:10.1038/s41467-024-46068-3
PMID:38396116
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10891081/
Abstract

Microglia nodules (HLA-DR cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology. Compared to microglia nodules in stroke, those in MS show enhanced expression of genes previously found upregulated in MS lesions. Furthermore, genes associated with lipid metabolism, presence of T and B cells, production of immunoglobulins and cytokines, activation of the complement cascade, and metabolic stress are upregulated in microglia nodules in MS. Compared to stroke, they more frequently phagocytose oxidized phospholipids and possess a more tubular mitochondrial network. Strikingly, in MS, some microglia nodules encapsulate partially demyelinated axons. Taken together, we propose that activation of microglia nodules in MS by cytokines and immunoglobulins, together with phagocytosis of oxidized phospholipids, may lead to a microglia phenotype prone to MS lesion formation.

摘要

小胶质细胞结节（HLA-DR 细胞簇）与脑病理学有关。在这项尸检研究中，我们研究了它们是否代表多发性硬化症（MS）病变形成的第一阶段。我们表明，小胶质细胞结节与更严重的 MS 病理学有关。与中风中的小胶质细胞结节相比，MS 中的小胶质细胞结节表现出先前在 MS 病变中上调的基因的增强表达。此外，与脂质代谢、T 和 B 细胞存在、免疫球蛋白和细胞因子产生、补体级联激活以及代谢应激相关的基因在 MS 中的小胶质细胞结节中上调。与中风相比，它们更频繁地吞噬氧化磷脂，并具有更管状的线粒体网络。值得注意的是，在 MS 中，一些小胶质细胞结节包裹部分脱髓鞘的轴突。综上所述，我们提出 MS 中小胶质细胞结节的激活是由细胞因子和免疫球蛋白引起的，再加上氧化磷脂的吞噬作用，可能导致易于形成 MS 病变的小胶质细胞表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/29f87ff65e8a/41467_2024_46068_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/fe5d0cd2b8b8/41467_2024_46068_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/98c87a62dbbe/41467_2024_46068_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/77644ca2f60c/41467_2024_46068_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/29f87ff65e8a/41467_2024_46068_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/f14d53004720/41467_2024_46068_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/a00c2ee64023/41467_2024_46068_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/fe5d0cd2b8b8/41467_2024_46068_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/98c87a62dbbe/41467_2024_46068_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/77644ca2f60c/41467_2024_46068_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59c3/10891081/29f87ff65e8a/41467_2024_46068_Fig7_HTML.jpg

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