Neuromodulation of Pancreatic Lymph Nodes as a Therapy for Type 1 Diabetes: An Anatomical Study on the Presence of a Neuro-Immune Link in Human Pancreatic Lymph Nodes and Potential Sites for Electrical Stimulation

IF 3.7 3区医学 Q2 CLINICAL NEUROLOGY

Neuromodulation Pub Date : 2026-10-01 Epub Date: 2026-02-24 DOI:10.1016/j.neurom.2025.12.009

Dyonne A.M. Koopmans-Lotgerink Bruinenberg MSc, Claire Mackaaij BSc, Eric Irwin PhD, Daniel J. Chew PhD, Isha Gupta PhD, Ronald L.A.W. Bleys PhD, Cindy G.J. Cleypool PhD

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引用次数: 0

Abstract

Objectives

Experimental studies in nonobese diabetic mice show that electrical stimulation of sympathetic nerves innervating pancreatic lymph nodes (LNs) reduces T cell activation through β-2 adrenergic signaling and limits further β-cell destruction. Neuromodulation of pancreatic LNs may therefore represent a novel therapeutic approach for early-stage type 1 diabetes (T1D) in humans. This study aims to explore the presence of a sympathetic neuro-immune link in human pancreatic LNs and to identify surgically accessible neuromodulation sites.

Materials and Methods

Upstream pancreatic LNs 8a and 8p were selected as primary targets because they drain lymph from multiple downstream pancreatic LNs. The suitability of two potential stimulation sites to target the sympathetic innervation of these LNs, being the LN capsule and the nerve plexus surrounding the proximal common hepatic artery (CHA), was evaluated. Ten formaldehyde-fixed human cadavers were studied, and various techniques were used to collect macro- and microscopic data on pancreatic LNs and the proximal CHA with its surrounding nerve plexus.

Results

Human pancreatic LNs contain sympathetic nerves in both their capsule and parenchyma, the latter occasionally as discrete nerves located close to T cells. Of the two upstream LNs studied, LN 8a was consistently present, easily accessible, and showed clear sympathetic connections to the celiac and CHA nerve plexuses. However, its position varied, and it was located near the pancreas. The nerve plexus around the CHA was consistently observed and contained predominantly sympathetic nerves, with nerves to LN 8a originating from its anterior-caudal region.

Conclusion

Human pancreatic LNs contain a sympathetic neuro-immune link that could be targeted for T1D treatment. The proximal CHA’s nerve plexus appears the most promising neuromodulation site owing to its surgical accessibility, sympathetic predominance, and suitability for safe device implantation.

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胰腺淋巴结的神经调节作为1型糖尿病的治疗：人类胰腺淋巴结和电刺激潜在部位存在神经免疫联系的解剖学研究

目的：非肥胖糖尿病小鼠的实验研究表明，电刺激支配胰腺淋巴结的交感神经通过β-2肾上腺素能信号传导减少T细胞的激活，并限制β细胞的进一步破坏。因此，胰腺LNs的神经调节可能代表了人类早期1型糖尿病（T1D）的一种新的治疗方法。本研究旨在探索人类胰腺ln中交感神经-免疫联系的存在，并确定手术可达的神经调节位点。材料和方法：选择上游胰腺l8a和8p作为主要靶点，因为它们从多个下游胰腺l5中引流淋巴。我们评估了LN囊和肝总动脉近端周围的神经丛这两个潜在刺激点对这些LN交感神经支配的适宜性。研究了10具甲醛固定的人尸体，并采用各种技术收集了胰腺LNs和近端CHA及其周围神经丛的宏观和微观数据。结果：人类胰腺的被膜和实质中都含有交感神经，后者偶尔是位于T细胞附近的离散神经。在研究的两个上游LNs中，ln8a始终存在，易于接近，并显示出与乳糜泻和CHA神经丛的清晰交感连接。然而，它的位置不同，它位于胰腺附近。CHA周围的神经丛一直被观察到，主要包含交感神经，LN 8a的神经起源于其前尾侧区。结论：人类胰腺ln含有交感神经免疫联系，可靶向治疗T1D。CHA近端神经丛是最有希望的神经调节部位，因为其手术可及性、交感优势和安全装置植入的适宜性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuromodulation 医学-临床神经学

CiteScore

6.40

自引率

3.60%

发文量

978

审稿时长

54 days

期刊介绍： Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational, and basic science research in the field. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer-reviewed articles on the technology, science, and clinical application of devices that interface with the nervous system to treat disease and improve function.