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

• Published in: Acta diabetologica Vol. 61; no. 9; pp. 1117 - 1127
• Main Authors: Tegehall, Angie, Ingvast, Sofie, Krogvold, Lars, Dahl-Jørgensen, Knut, Korsgren, Olle
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.09.2024; Springer Nature B.V
• Subjects: Adolescent; Adult; alpha-Defensins - genetics; alpha-Defensins - metabolism; Antibodies; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Antimicrobial agents; Antimicrobial Cationic Peptides - metabolism; Bacteria; Bacterial infections; beta-Defensins - genetics; beta-Defensins - metabolism; Biologi med inriktning mot molekylär immunologi; Biology with specialization in Molecular Immunology; Biopsy; Blood & organ donations; Cathelicidins; CD3 antigen; CD45 antigen; Defensins; Defensins - genetics; Defensins - metabolism; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Etiopathology; Female; Gram-positive bacteria; Humans; Immune response; Immune system; Immunity, Innate; Inflammation; Innate immunity; Internal Medicine; Leukocytes (granulocytic); Leukocytes (neutrophilic); Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - metabolism; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Organ donors; Original; Original Article; Pancreas; Pancreas - immunology; Pancreas - metabolism; Pancreas - pathology; Small intestine; Spleen; Statistical analysis; Type 1 diabetes; Young Adult; United States > US; Germany; California; Innate immunity; Etiopathology; Defensins; Pancreas; Biopsy; 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.