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健康供者与早发性关节炎患者衰老相关生物标志物的对比研究。VPAC 受体分析及其影响。

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

机构信息

Departamento de Biología Celular, Facultad de Biología y Medicina, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, 28040 Madrid, Spain.

Servicio de Reumatología, Instituto de Investigación Sanitaria Hospital La Princesa (IIS-IP), 28006 Madrid, Spain.

出版信息

Cells. 2020 Dec 4;9(12):2592. doi: 10.3390/cells9122592.

DOI:10.3390/cells9122592
PMID:33291545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7761848/
Abstract

Pro-inflammatory CD4CD28 T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4CD28 T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4CD28 T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4CD28 T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4CD28 T cells showed higher expression of VPAC and lower of VPAC, VPAC showing a significant increased expression in EA cells. Sorted CD4CD28 T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis.

摘要

促炎 CD4CD28 T 细胞是免疫衰老的特征，但也是几种自身免疫性/炎症性疾病的特征。血管活性肠肽（VIP）作为一种抗炎和免疫调节介质作用于这些细胞。我们的目的是研究衰老 Th 细胞和 VIP 轴在早期关节炎（EA）中的相互影响，并与非 EA 供体进行比较。我们通过实时 PCR 来描述衰老 Th 细胞与 EA 的临床参数之间的相关性以及衰老 Th 标志物的行为。在基线和 6 个月的随访时系统地记录临床数据。通过分选测量的 CD4CD28 T 细胞数量在最初符合类风湿关节炎（RA）ACR 分类标准的患者中高于被归类为未分化关节炎（UA）的患者。发现 EA CD4CD28 T 细胞与 CRP 或 ESR 之间存在轻微的正相关，与骨密度呈负相关。EA CD4CD28 T 细胞中的 Th 衰老标志物与供体相似，但其中一些在 6 个月的随访后增加。通过实时 PCR 和免疫荧光分析 VPAC 受体，CD4CD28 T 细胞显示出更高的 VPAC 表达和更低的 VPAC 表达，VPAC 在 EA 细胞中表达显著增加。在 VIP 存在的情况下体外分选 CD4CD28 T 细胞扩增，其中 VIP 增加了衰老标志物 CD27，而减少了 CD57 或 NKG2 衰老标志物。我们的研究首次证明了衰老 Th 细胞和 VIP 轴之间存在联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/9d67d52972f3/cells-09-02592-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/4f469c591268/cells-09-02592-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/56f98dbadfd1/cells-09-02592-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/9d67d52972f3/cells-09-02592-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/4f469c591268/cells-09-02592-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/a43dce5e5adc/cells-09-02592-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/eb2edf6f761b/cells-09-02592-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/430a30f7f5c4/cells-09-02592-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/56f98dbadfd1/cells-09-02592-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/bb69797eb9ca/cells-09-02592-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae4/7761848/9d67d52972f3/cells-09-02592-g007.jpg

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Int J Mol Sci. 2019 Dec 20;21(1):65. doi: 10.3390/ijms21010065.
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Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype.
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衰老的滑膜成纤维细胞在类风湿性关节炎组织中过早积累，并表现出增强的炎症表型。
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