Mechanisms of diabetic autoimmunity: I—the inductive interface between islets and the immune system at onset of inflammation

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• 作者：Nadir Askenasy
• 关键词：Type 1 diabetes onset ; Thymus ; Islets ; Pancreatic lymph nodes ; Neonatal lymphopenia ; Diabetogenic cells ; T cell effectors
• 刊名：Immunologic Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：64
• 期：2
• 页码：360-368
• 全文大小：848 KB
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• 作者单位：Nadir Askenasy (1)
  
  1. The Leah and Edward M. Frankel Laboratory of Experimental Bone Marrow Transplantation, 14 Kaplan Street, 49202, Petach Tikva, Israel
  
• 刊物主题：Allergology; Immunology; Medicine/Public Health, general; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-0755

文摘

The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.