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系统性硬化症患者的 6-硫酸乳糖胺单核细胞在数量和功能上受到干扰。

6-Sulfo LacNAc monocytes are quantitatively and functionally disturbed in systemic sclerosis patients.

机构信息

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France.

AP-HP, Hôpital Saint-Antoine, Service d'Hématologie clinique, Paris, France.

出版信息

Clin Exp Immunol. 2022 Aug 19;209(2):175-181. doi: 10.1093/cei/uxac059.

DOI:10.1093/cei/uxac059
PMID:35758259
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9390843/
Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, microangiopathy, and autoantibodies. We previously reported that circulating follicular helper T (cTfh) cells are increased in SSc and induce plasmablast differentiation. However, mechanisms leading to cTfh cell expansion and activation in SSc remain to be established. Tfh cells require IL-12 for their expansion and differentiation. 6-Sulfo LacNAc monocytes (slanMo), a subset of monocytes, have a higher capacity to produce IL-12 and to induce CD4+ T cell proliferation in comparison with dendritic cells (DC) or classical monocytes. The aim of this study was to perform a quantitative and functional analysis of monocytes and DC and to correlate them with cTfh cell expansion and clinical manifestations in SSc. Using flow cytometry, we analyzed different monocyte subsets including slanMo and DC from 36 SSc patients and 26 healthy controls (HC). In vitro culture experiments of sorted slanMo were performed for functional analysis and cytokine production. We observed that slanMo, intermediate and non-classical monocytes were increased in SSc in comparison with HC. Furthermore, the increase in slanMo cells was more potent in patients with diffuse SSc. We observed a significant positive correlation between slanMo and cTfh cell levels in SSc patients but not in HC. Other monocyte subsets did not correlate with cTfh cell expansion. In addition, we observed that in vitro, slanMo cells from SSc patients produced less IL-12 than slanMo from HC. SlanMo are increased in SSc and may participate in the activation of cTfh cells in SSc.

摘要

系统性硬化症(SSc)是一种自身免疫性疾病,其特征为纤维化、微血管病变和自身抗体。我们之前报道过,循环滤泡辅助 T 细胞(cTfh)在 SSc 中增加,并诱导浆母细胞分化。然而,导致 SSc 中 cTfh 细胞扩增和激活的机制仍有待确定。Tfh 细胞需要 IL-12 才能扩增和分化。6-硫酸乳糖-N-乙酰氨基葡萄糖(6-Sulfo LacNAc)单核细胞(slanMo)是单核细胞的一个亚群,与树突状细胞(DC)或经典单核细胞相比,其产生 IL-12 和诱导 CD4+T 细胞增殖的能力更高。本研究旨在对单核细胞和 DC 进行定量和功能分析,并将其与 SSc 中的 cTfh 细胞扩增和临床表现相关联。我们使用流式细胞术分析了 36 名 SSc 患者和 26 名健康对照者(HC)的不同单核细胞亚群,包括 slanMo 和 DC。对分选的 slanMo 进行体外培养实验以进行功能分析和细胞因子产生。我们观察到 slanMo、中间型和非经典单核细胞在 SSc 中比 HC 增加。此外,弥漫性 SSc 患者的 slanMo 细胞增加更为明显。我们观察到 SSc 患者的 slanMo 细胞与 cTfh 细胞水平之间存在显著正相关,但在 HC 中没有。其他单核细胞亚群与 cTfh 细胞扩增无关。此外,我们观察到 SSc 患者的 slanMo 细胞体外产生的 IL-12 少于 HC 的 slanMo 细胞。SlanMo 在 SSc 中增加,并可能参与 SSc 中 cTfh 细胞的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c98a/9390843/e604e75996c9/uxac059f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c98a/9390843/e604e75996c9/uxac059f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c98a/9390843/e604e75996c9/uxac059f0004.jpg

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本文引用的文献

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Adv Rheumatol. 2021 May 22;61(1):27. doi: 10.1186/s42358-021-00182-8.
2
Integrated bulk and single-cell RNA-sequencing identified disease-relevant monocytes and a gene network module underlying systemic sclerosis.整合批量和单细胞 RNA 测序鉴定了与疾病相关的单核细胞和系统性硬化症的基因网络模块。
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T Follicular Helper Cell Biology: A Decade of Discovery and Diseases.
滤泡辅助性 T 细胞生物学:十年的发现与疾病
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Pathophysiology of systemic sclerosis: current understanding and new insights.系统性硬化症的病理生理学:当前认识和新见解。
Expert Rev Clin Immunol. 2019 Jul;15(7):753-764. doi: 10.1080/1744666X.2019.1614915. Epub 2019 May 13.
5
Circulating follicular helper T cells are increased in systemic sclerosis and promote plasmablast differentiation through the IL-21 pathway which can be inhibited by ruxolitinib.循环滤泡辅助 T 细胞在系统性硬化症中增加,并通过 IL-21 途径促进浆母细胞分化,而 ruxolitinib 可抑制该途径。
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6
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