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血管活性肠肽轴在格雷夫斯病患者中功能失调。

Vasoactive intestinal peptide axis is dysfunctional in patients with Graves' disease.

机构信息

Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Calle José Antonio Novais, 12, 28040, Madrid, Spain.

Servicio de Endocrinología Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, 28006, Madrid, Spain.

出版信息

Sci Rep. 2020 Aug 3;10(1):13018. doi: 10.1038/s41598-020-70138-3.

DOI:10.1038/s41598-020-70138-3
PMID:32747757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7400547/
Abstract

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves' disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto's thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.

摘要

血管活性肠肽 (VIP) 是一种具有强大免疫调节特性的神经肽。血清 VIP 水平降低和免疫细胞上的 VIP 受体/信号转导改变与不同的炎症/自身免疫性疾病有关。然而，其在自身免疫性甲状腺疾病 (AITD) 中的作用尚不清楚。本研究探讨了 AITD 患者外周免疫细胞中 VIP 系统、自身免疫背景和甲状腺激素之间的相互关系。只有格雷夫斯病 (GD) 患者的血清 VIP 水平明显低于健康受试者和桥本甲状腺炎患者。GD 患者在发病时的血清 VIP 水平较低，与甲状腺激素水平呈显著负相关。GD 患者外周血单个核细胞 (PBMC) 中 VIP 受体 VPAC1 和 VPAC2 的表达明显上调。这些患者的 VIP 信号转导受损，可能归因于 VPAC1 功能障碍而 VPAC2 保留。GD 患者中健康受试者 PBMC 中 VPAC1 和甲状腺激素受体表达之间的相关性丧失。总之，GD 患者外周免疫细胞中的 VIP 系统发生改变，这一发现与不同的甲状腺激素受体模式相关，表明 VIP 在这种情况下具有动态的相互调节作用和突出的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/00f1e6df0e10/41598_2020_70138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/78f3f9496b6a/41598_2020_70138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/ebcf830988cb/41598_2020_70138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/80aa19d3c8e9/41598_2020_70138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/00f1e6df0e10/41598_2020_70138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/78f3f9496b6a/41598_2020_70138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/ebcf830988cb/41598_2020_70138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/80aa19d3c8e9/41598_2020_70138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1756/7400547/00f1e6df0e10/41598_2020_70138_Fig4_HTML.jpg

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