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Objective and design <p>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.</p> Material <p>Congenic prediabetes BB Gimap5-DP and control Gimap5-DR (Diabetes Resistant) rats were followed every other day from 29 to 32&#xa0;days of age until peak serum IgE (≤ 55&#xa0;days of age).</p> Methods <p>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.</p> Results <p>Serum IgE levels increased with age in normoglycemic BB Gimap5-DP rats. Quantification of infiltrating cells per mm<sup>2</sup> 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 <i>Gimap4</i> and <i>Gimap5</i>.</p> Conclusions <p>Elevated IgE levels herald T lymphocyte and macrophage infiltration. Pancreatic islet inflammation was linked to <i>Gimap4</i>, <i>Gimap5,</i> and other potential candidate genes on rat chromosome 4.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月3日

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

摘要

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.