Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes [Review]
| Autor: | Shoichiro Tanaka, Yoriko Nishida, Tetsuro Kobayashi, Kaoru Aida |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
geography
geography.geographical_feature_category Innate immune system Cell Death Endocrinology Diabetes and Metabolism Pattern recognition receptor Biology Acquired immune system Islet Fas ligand Islets of Langerhans Diabetes Mellitus Type 1 Endocrinology Immune system Leukemic Infiltration Receptors Pattern Recognition Immunology Humans CXCL10 Cytotoxic T cell Interferons Pancreas Enterovirus |
| Zdroj: | Endocrine Journal. 60:837-845 |
| ISSN: | 1348-4540 0918-8959 |
| Popis: | Fulminant type 1 diabetes is characterized by a rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetic complications. This review summarizes new findings related to the pathophysiology of accelerated β-cell failure in fulminant type 1 diabetes. Immunohistological examination revealed the presence of enterovirus in pancreatic islet cells and exocrine tissues and hyperexpression of pattern recognition receptors (PRRs) including melanoma differentiation-associated antigen 5 (MDA5), retinoic acid-inducible gene-I (RIG-I), Toll-like receptor (TLR)3 and TLR4, essential sensors of innate immunity, in islet cells and mononuclear cells (MNCs) infiltrating islets. Interferon (IFN)-α and IFN-β, products of PRR cascades, were expressed in both islet cells and infiltrating MNCs. Phenotypes of infiltrating cells around and/or into islets were mainly dendritic cells, macrophages and CD8+ T cells. Islet β-cells simultaneously expressed CXC chemokine ligand 10 (CXCL10), IFN-γ and interleukin-18, indicating that these chemokines/ cytotoxic cytokines mutually amplify their cytoplasmic expression in the islet cells. These positive feedback systems might enhance adaptive immunity, leading to rapid and complete loss of β-cells in fulminant type 1 diabetes. In innate and adaptive/autoimmune immune processes, the mechanisms behind bystander activation/killing might further amplify β-cell destruction. In addition to intrinsic pathway of cell apoptosis, the Fas and Fas ligand pathway are also involved as an extrinsic pathway of cell apoptosis. A high prevalence of anti-amylase autoantibodies was recognized in patients with fulminant type 1 diabetes, which suggests that Th2 T-cell reactive immunity against amylase might contribute to β-cell destruction in fulminant type 1 diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|