Insulitis and aging: Immune cell dynamics in Langerhans islets
With increasing age, the risk for age-related type-2-diabetes also increases due to impaired glucose tolerance and insulin secretion. This disease process may be influenced by various factors, including immune cell triggered inflammation and fibrosis. Although immune cells are a necessary component...
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Elsevier
2025-05-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001004 |
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| author | Julia Jelleschitz Sophie Heider Richard Kehm Patricia Baumgarten Christiane Ott Vanessa Schnell Tilman Grune Annika Höhn |
| author_facet | Julia Jelleschitz Sophie Heider Richard Kehm Patricia Baumgarten Christiane Ott Vanessa Schnell Tilman Grune Annika Höhn |
| author_sort | Julia Jelleschitz |
| collection | DOAJ |
| description | With increasing age, the risk for age-related type-2-diabetes also increases due to impaired glucose tolerance and insulin secretion. This disease process may be influenced by various factors, including immune cell triggered inflammation and fibrosis. Although immune cells are a necessary component of islets, little is known about immune cell accumulation, immune cell subtype shifts and subsequent influence on glucose metabolism in healthy aging. However, this is critical for understanding the mechanisms that influence β-cell health. Therefore, we studied young and old male C57BL/6J mice, focusing on immune cell composition, patterns of accumulation, and the presence of fibrosis within the pancreatic islets.Our findings demonstrate that insulitis occurs in healthy aged mice without immediate development of a diabetic phenotype. Aged islets exhibited an increase in leukocytes and a shift in immune cell composition. While insulitis typically involves excessive immune cell accumulation, we observed a moderate increase in macrophages and T-cells during aging, which may support β-cell proliferation via cytokine secretion. In fact, aged mice in our study showed an increase in β-cell mass as well as a partially higher insulin secretory capacity, which compensated for the loss of β-cell functionality in insulitic islets and led to improved glucose tolerance. Furthermore, fibrosis which is normally triggered by immune cells, increased with age but appears to reach a steady state, emphasizing the importance of counter-regulatory mechanisms and immune system regulation.Our results suggest, that immune cell subtypes change with age and that non-pathological accumulation of immune-cells may regulate glucose metabolism through secretion of cytokines. |
| format | Article |
| id | doaj-art-c586d5586bab479b8f15b0ad1862dafb |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | Redox Biology |
| spelling | doaj-art-c586d5586bab479b8f15b0ad1862dafb2025-08-20T02:24:45ZengElsevierRedox Biology2213-23172025-05-018210358710.1016/j.redox.2025.103587Insulitis and aging: Immune cell dynamics in Langerhans isletsJulia Jelleschitz0Sophie Heider1Richard Kehm2Patricia Baumgarten3Christiane Ott4Vanessa Schnell5Tilman Grune6Annika Höhn7Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; DZHK (German Center for Cardiovascular Research), Partner site Berlin, Berlin, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; DZHK (German Center for Cardiovascular Research), Partner site Berlin, Berlin, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; DZHK (German Center for Cardiovascular Research), Partner site Berlin, Berlin, GermanyDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Corresponding author. German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.With increasing age, the risk for age-related type-2-diabetes also increases due to impaired glucose tolerance and insulin secretion. This disease process may be influenced by various factors, including immune cell triggered inflammation and fibrosis. Although immune cells are a necessary component of islets, little is known about immune cell accumulation, immune cell subtype shifts and subsequent influence on glucose metabolism in healthy aging. However, this is critical for understanding the mechanisms that influence β-cell health. Therefore, we studied young and old male C57BL/6J mice, focusing on immune cell composition, patterns of accumulation, and the presence of fibrosis within the pancreatic islets.Our findings demonstrate that insulitis occurs in healthy aged mice without immediate development of a diabetic phenotype. Aged islets exhibited an increase in leukocytes and a shift in immune cell composition. While insulitis typically involves excessive immune cell accumulation, we observed a moderate increase in macrophages and T-cells during aging, which may support β-cell proliferation via cytokine secretion. In fact, aged mice in our study showed an increase in β-cell mass as well as a partially higher insulin secretory capacity, which compensated for the loss of β-cell functionality in insulitic islets and led to improved glucose tolerance. Furthermore, fibrosis which is normally triggered by immune cells, increased with age but appears to reach a steady state, emphasizing the importance of counter-regulatory mechanisms and immune system regulation.Our results suggest, that immune cell subtypes change with age and that non-pathological accumulation of immune-cells may regulate glucose metabolism through secretion of cytokines.http://www.sciencedirect.com/science/article/pii/S2213231725001004Langerhans isletsAgingInsulitisFibrosisImmune cells |
| spellingShingle | Julia Jelleschitz Sophie Heider Richard Kehm Patricia Baumgarten Christiane Ott Vanessa Schnell Tilman Grune Annika Höhn Insulitis and aging: Immune cell dynamics in Langerhans islets Redox Biology Langerhans islets Aging Insulitis Fibrosis Immune cells |
| title | Insulitis and aging: Immune cell dynamics in Langerhans islets |
| title_full | Insulitis and aging: Immune cell dynamics in Langerhans islets |
| title_fullStr | Insulitis and aging: Immune cell dynamics in Langerhans islets |
| title_full_unstemmed | Insulitis and aging: Immune cell dynamics in Langerhans islets |
| title_short | Insulitis and aging: Immune cell dynamics in Langerhans islets |
| title_sort | insulitis and aging immune cell dynamics in langerhans islets |
| topic | Langerhans islets Aging Insulitis Fibrosis Immune cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001004 |
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