Using GeoMx DSP Spatial Proteomics to Investigate Immune Infiltration of NOD Mouse Islet and Exocrine Compartments.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Molecular Imaging and Biology Pub Date : 2024-11-18 DOI:10.1007/s11307-024-01961-7

Hasim Tekin, Claes Lindhardt, Julie Christine Antvorskov, Nicolai Schou Bager, Signe Regner Michaelsen, Aušrinė Areškevičiūtė, Jonas Pordel Vind, Bjarne Winther Kristensen, Knud Josefsen

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Abstract

Purpose: Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration has a heterogenic nature that isn't described in detail, as not all islets are infiltrated. The aim of this study was to investigate if the observed heterogeneity is coupled to differences in immune and/or dysfunctional status of islets or exocrine cells, and if specific markers could elucidate mechanistic details of T1D pathogenesis.

Procedures: The GeoMx platform was used to spatially quantify protein levels in pancreatic islets and exocrine tissue in Non-Obese Diabetic (NOD) mice. The protein panel included 17 immune activity markers and nine dysfunction markers. Immunohistochemical (IHC) staining and digital image analysis was used to analyze select marker proteins.

Results: Use of the GeoMx platform to investigate T1D was shown to be possible, as Granzyme B protein levels were found to be lower in distal islet areas when compared to proximal areas. Smooth Muscle Actin protein levels were higher in exocrine areas proximal to immune-infiltrated islets, when compared to distally located exocrine areas. Findings from GeoMx were however not observed in IHC-stained sections.

Conclusions: This study demonstrates that investigating T1D is possible with spatial proteomics, as the assays revealed presence of heterogenic islet areas in NOD mice, which may play a role in T1D progression and escape from immune recognition. This study highlights the potential of spatial technologies for elucidating T1D pathogenesis and future treatment strategies.

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利用 GeoMx DSP 空间蛋白质组学研究 NOD 小鼠胰岛和外分泌区的免疫渗透。

目的：1 型糖尿病（T1D）的发病机制包括免疫细胞浸润胰腺朗格汉斯胰岛，导致 T 细胞活化、β 细胞破坏和胰岛素分泌受损。然而，由于并非所有的胰岛都会受到浸润，因此浸润具有异质性，尚未得到详细描述。本研究的目的是调查所观察到的异质性是否与胰岛或外分泌细胞的免疫和/或功能失调状态的差异有关，以及特定标记物是否能阐明 T1D 发病机制的细节：利用 GeoMx 平台对非肥胖糖尿病（NOD）小鼠胰岛和外分泌组织中的蛋白质水平进行空间定量。蛋白质面板包括 17 种免疫活性标记物和 9 种功能障碍标记物。免疫组织化学（IHC）染色和数字图像分析用于分析选定的标记蛋白质：结果：利用 GeoMx 平台研究 T1D 是可行的，因为与近端区域相比，远端胰岛区域的颗粒酶 B 蛋白水平较低。与远端外分泌区域相比，免疫浸润胰岛近端外分泌区域的平滑肌肌动蛋白水平较高。然而，在 IHC 染色切片中未观察到 GeoMx 的结果：本研究表明，利用空间蛋白质组学研究 T1D 是可行的，因为检测结果显示 NOD 小鼠体内存在异源性胰岛区，这可能在 T1D 的发展和逃避免疫识别中发挥作用。这项研究凸显了空间技术在阐明T1D发病机制和未来治疗策略方面的潜力。

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

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.