Vasoactive intestinal peptide axis is dysfunctional in patients with Graves\u2019 disease

M Carrión,I González-Álvaro,A Serrano-Somavilla,I V Seoane,Mónica Marazuela,Rosa P Gomariz,A M Ramos-Leví,Y Juarranz,D Castro,R Martínez-Hernández

doi:10.1038/s41598-020-70138-3

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.

Highlights

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties
Once confirmed that serum VIP levels were only reduced in hyperthyroid Graves’ disease (GD) patients and given that we hypothesized that the alterations of thyroid hormone system might be interrelated with the VIP axis, we examined the expression and functionality of VIP receptors in peripheral blood mononuclear cells (PBMC) from both euthyroid and hyperthyroid GD patients
We describe that VIP serum levels are significantly reduced in GD patients at the onset of the disease, when thyroid hormone levels are elevated

Summary

Introduction

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. 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. Experimental data and clinical observations in animal models and humans point to an important role of interactions between neuroendocrine and immune systems for the maintenance of the overall h omeostasis[1,2] This bidirectional network is functionally supported by the presence of shared signalling molecules, including hormones, neuropeptides, cytokines, and their respective receptors. HT represents the archetype for T-cell-mediated degenerative diseases It is characterized by a progressive autoimmune thyrocyte depletion, resulting in impaired thyroid hormone production and clinical hypothyroidism[9]

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