Reduced expression of central innate defense molecules in pancreatic biopsies from subjects with Type  1 diabetes

• Published in: Acta diabetologica 2024, Vol.61 (9), p.1117-1127
• Main Authors: Tegehall, Angie, Ingvast, Sofie, Krogvold, Lars, Dahl-Jørgensen, Knut, Korsgren, Olle
• Format: Article
• Language: English
• Subjects: Biologi med inriktning mot molekylär immunologi; Biology with specialization in Molecular Immunology; Biopsy; CD3 antigen; CD45 antigen; Defensins; Diabetes; Diabetes mellitus (insulin dependent); Etiopathology; Immune system; Inflammation; Innate immunity; Internal Medicine; Leukocytes (granulocytic); Leukocytes (neutrophilic); Lymphocytes T; Macrophages; Medicine; Medicine & Public Health; Metabolic Diseases; Organ donors; Original; Original Article; Pancreas; Type 1 diabetes
• ISSN: 1432-5233; 0940-5429; 1432-5233
• DOI: 10.1007/s00592-024-02286-1

Aims/Hypothesis Defensins play a crucial role in the innate immune system's first defense against microbial threats. However, little is known about the defensin system in the pancreas, especially in relation to Type 1 diabetes. We explore the expression of defensins in different disease stages of Type 1 diabetes and correlated obtained findings to the degree of inflammation, providing new insights into the disease and the innate immune system. Material and methods Pancreases from non-diabetic human organ donors of different age groups and donors with Type 1 diabetes with different disease duration were examined. Sections from head, body and tail of the pancreas were stained for eight different defensins and for immune cells; CD3+, CD45+, CD68+ and NES+ (granulocytes). Results In non-diabetic adult controls the level of expression for defensins Beta-1,Alpha-1, Cathelicidin and REG3A correlated with the level of inflammation. In contrast, individuals with Type  1 diabetes exhibit a reduction or absence of several central defensins regardless of the level of inflammation in their pancreas. The expression of Cathelicidin is present in neutrophils and macrophages but not in T-cells in subjects with Type 1 diabetes. Conclusions Obtained findings suggest a pancreatic dysfunction in the innate immune system and the bridging to the adaptive system in Type 1 diabetes. Further studies on the role of the local innate immune system in Type 1 diabetes is needed.