Quantitative temporal analysis of pancreatic islet T lymphocyte and macrophage infiltration heralded by serum IgE in congenic BioBreeding (BB) Gimap5^-/^- rats at risk for insulitis and acute onset diabetes.

IF 5.4 3区医学 Q2 CELL BIOLOGY

Inflammation Research Pub Date : 2025-10-03 DOI:10.1007/s00011-025-02101-9

Josefine Jönsson, Linda Faxius, Jeanette Tångrot, Krysten Vance, Stephanie Jerman, Doug Bowman, Marika Bogdani, Peter Ericsson, Rasmus Bennet, Anita Ramelius, Åke Lernmark

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Abstract

Objective and design: The objective was to determine the association between serum IgE levels and the infiltration order of T lymphocytes and macrophages in pancreatic islets in relation to the loss of insulin and glucagon cells in presymptomatic congenic BB Gimap5-DP (Diabetes Prone) rats.

Material: Congenic prediabetes BB Gimap5-DP and control Gimap5-DR (Diabetes Resistant) rats were followed every other day from 29 to 32 days of age until peak serum IgE (≤ 55 days of age).

Methods: Serum IgE was measured using ELISA. The HALO™ platform facilitated quantitative image analysis of infiltrating T lymphocytes, macrophages, and target organ insulin and glucagon cells. Whole genome sequencing (WGS) was employed to identify candidate type 1 diabetes genes.

Results: Serum IgE levels increased with age in normoglycemic BB Gimap5-DP rats. Quantification of infiltrating cells per mm² in and around the islets indicated that T lymphocytes are the initial infiltrators, followed by macrophages. Elevated serum IgE levels inversely correlated with beta-cell mass (total mg insulin/mg pancreas). WGS refined the risk segment for islet inflammation to 1.02 Mbp, leaving 10 candidate genes, including Gimap4 and Gimap5.

Conclusions: Elevated IgE levels herald T lymphocyte and macrophage infiltration. Pancreatic islet inflammation was linked to Gimap4, Gimap5, and other potential candidate genes on rat chromosome 4.

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血清IgE对先天性生物繁殖（BB） Gimap5-/-大鼠胰岛T淋巴细胞和巨噬细胞浸润的影响

目的和设计：目的是确定血清IgE水平与T淋巴细胞和巨噬细胞在胰岛的浸润顺序与症状前先天性BB Gimap5-DP（糖尿病易发）大鼠胰岛素和胰高血糖素细胞损失的关系。材料：从29 ~ 32日龄，每隔一天对先天性糖尿病前期BB大鼠Gimap5-DP和对照大鼠Gimap5-DR（糖尿病抵抗）进行随访，直至血清IgE达到峰值（≤55日龄）。方法：采用ELISA法测定血清IgE。HALO™平台有助于对浸润的T淋巴细胞、巨噬细胞、靶器官胰岛素和胰高血糖素细胞进行定量图像分析。采用全基因组测序（WGS）技术鉴定1型糖尿病候选基因。结果：血糖正常的BB Gimap5-DP大鼠血清IgE水平随年龄增长而升高。胰岛内及周围每mm2浸润细胞计数表明，T淋巴细胞是最初的浸润细胞，其次是巨噬细胞。血清IgE水平升高与β细胞质量（总胰岛素mg /胰腺mg）呈负相关。WGS将胰岛炎症的风险片段细化到1.02 Mbp，留下10个候选基因，包括Gimap4和Gimap5。结论：IgE水平升高预示T淋巴细胞和巨噬细胞浸润。胰岛炎症与大鼠4号染色体上的Gimap4、Gimap5和其他潜在候选基因有关。

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

Inflammation Research 医学-免疫学

CiteScore

9.90

自引率

1.50%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.