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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.

Jönsson, Josefine LU orcid ; Faxius, Linda LU ; Tångrot, Jeanette ; Vance, Krysten ; Jerman, Stephanie ; Bowman, Doug ; Bogdani, Marika ; Ericsson, Peter ; Bennet, Rasmus LU and Ramelius, Anita LU , et al. (2025) In Inflammation Research 74(1).
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... (More)

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 mm
2 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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organization
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type
Contribution to journal
publication status
published
subject
keywords
Animals, Immunoglobulin E/blood, Macrophages/immunology, Islets of Langerhans/immunology, T-Lymphocytes/immunology, Diabetes Mellitus, Type 1/immunology, Male, Rats, Inbred BB, Rats, Insulin/metabolism, Prediabetic State/immunology, Glucagon/metabolism, Animals, Congenic
in
Inflammation Research
volume
74
issue
1
article number
134
publisher
Birkhäuser
external identifiers
  • pmid:41042382
ISSN
1420-908X
DOI
10.1007/s00011-025-02101-9
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
7c431e9c-95ae-4b1f-b30c-6c1e2c904371
date added to LUP
2025-10-04 11:38:24
date last changed
2025-10-07 03:14:02
@article{7c431e9c-95ae-4b1f-b30c-6c1e2c904371,
  abstract     = {{<p>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.</p><p>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).</p><p>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.</p><p>RESULTS: Serum IgE levels increased with age in normoglycemic BB Gimap5-DP rats. Quantification of infiltrating cells per mm<br>
 2 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.<br>
 </p><p>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.</p>}},
  author       = {{Jönsson, Josefine and Faxius, Linda and Tångrot, Jeanette and Vance, Krysten and Jerman, Stephanie and Bowman, Doug and Bogdani, Marika and Ericsson, Peter and Bennet, Rasmus and Ramelius, Anita and Lernmark, Åke}},
  issn         = {{1420-908X}},
  keywords     = {{Animals; Immunoglobulin E/blood; Macrophages/immunology; Islets of Langerhans/immunology; T-Lymphocytes/immunology; Diabetes Mellitus, Type 1/immunology; Male; Rats, Inbred BB; Rats; Insulin/metabolism; Prediabetic State/immunology; Glucagon/metabolism; Animals, Congenic}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Birkhäuser}},
  series       = {{Inflammation Research}},
  title        = {{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.}},
  url          = {{http://dx.doi.org/10.1007/s00011-025-02101-9}},
  doi          = {{10.1007/s00011-025-02101-9}},
  volume       = {{74}},
  year         = {{2025}},
}