Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit
| العنوان: | Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit |
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| المؤلفون: | Masako Suzuki, Yoriko Nishida, Taro Maruyama, Shoichiro Tanaka, Hiroki Shimura, Sayaka Arai-Yamashita, Toyoshi Endo, Akio Kawaguchi, Masahiro Kaneshige, Akira Shimada, Daiichiro Akiyama, Ryohei Katoh, Masashi Takahashi, Kaoru Aida, Soichi Takizawa, Tetsuro Kobayashi, Fumihiko Furuya |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Male, Chemokine, Receptors, CXCR3, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, CXCR3, Diabetic Ketoacidosis, Fatal Outcome, Insulin-Secreting Cells, MHC class I, Internal Medicine, medicine, Enterovirus Infections, CXCL10, Humans, Aged, Type 1 diabetes, geography, MHC class II, HLA-D Antigens, geography.geographical_feature_category, biology, Histocompatibility Antigens Class I, Middle Aged, medicine.disease, Islet, Chemokine CXCL10, Cytokine, Diabetes Mellitus, Type 1, Immunology, biology.protein, RNA, Viral, Original Article, Capsid Proteins, Female, Autopsy, Immunology and Transplantation |
| الوصف: | OBJECTIVE Fulminant type 1 diabetes is characterized by the rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetes complications. Causative mechanisms for accelerated β-cell failure are unclear. RESEARCH DESIGN AND METHODS Subjects comprised three autopsied patients who died from diabetic ketoacidosis within 2–5 days after onset of fulminant type 1 diabetes. We examined islet cell status, including the presence of enterovirus and chemokine/cytokine/major histocompatibility complex (MHC) expressions in the pancreata using immunohistochemical analyses and RT-PCR. RESULTS Immunohistochemical analysis revealed the presence of enterovirus-capsid protein in all three affected pancreata. Extensive infiltration of CXCR3 receptor–bearing T-cells and macrophages into islets was observed. Dendritic cells were stained in and around the islets. Specifically, interferon-γ and CXC chemokine ligand 10 (CXCL10) were strongly coexpressed in all subtypes of islet cells, including β-cells and α-cells. No CXCL10 was expressed in exocrine pancreas. Serum levels of CXCL10 were increased. Expression of MHC class II and hyperexpression of MHC class I was observed in some islet cells. CONCLUSIONS These results strongly suggest the presence of a circuit for the destruction of β-cells in fulminant type 1 diabetes. Enterovirus infection of the pancreas initiates coexpression of interferon-γ and CXCL10 in β-cells. CXCL10 secreted from β-cells activates and attracts autoreactive T-cells and macrophages to the islets via CXCR3. These infiltrating autoreactive T-cells and macrophages release inflammatory cytokines including interferon-γ in the islets, not only damaging β-cells but also accelerating CXCL10 generation in residual β-cells and thus further activating cell-mediated autoimmunity until all β-cells have been destroyed. |
| اللغة: | English |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::181ce142dedee35e2ac445f2d7db241aTest http://europepmc.org/articles/PMC2750208Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....181ce142dedee35e2ac445f2d7db241a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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