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.

Jönsson J, Faxius L, Tångrot J, Vance K, Jerman S, Bowman D, Bogdani M, Ericsson P, Bennet R, Ramelius A, Lernmark Å

Inflamm Res 74 (1) 134 [2025-10-03; online 2025-10-03]

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. 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). 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. 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. 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.

Bioinformatics (NBIS) [Collaborative]

Bioinformatics Support and Infrastructure [Collaborative]

Bioinformatics Support, Infrastructure and Training [Collaborative]

PubMed 41042382

DOI 10.1007/s00011-025-02101-9

Crossref 10.1007/s00011-025-02101-9

pmc: PMC12494634
pii: 10.1007/s00011-025-02101-9