Islet Glia, Neurons, and β Cells The Neuroimmune Interface in the Pathogenesis of  Type 1 Diabetes

• Published in: Annals of the New York Academy of Sciences Vol. 1150; no. 1; pp. 32 - 42
• Main Authors: Tsui, Hubert, Winer, Shawn, Chan, Yin, Truong, Dorothy, Tang, Lan, Yantha, Jason, Paltser, Geoffrey, Dosch, Hans‐Michael
• Format: Journal Article
• Language: English
• Published: 01.01.2008
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1447.033

Type 1 diabetes (T1D) is caused by autoimmune β cell destruction. The early events triggering T1D and the forces that keep diabetic autoimmunity pancreas specific have been unclear. Our discovery that autoimmune islet destruction is not β‐cell‐exclusive but includes cytotoxic T cell targeting of peri‐islet glia, evoked the possibility that T1D pathogenesis may involve neuronal elements beyond β cell/immune interactions. Recently, we have found that sensory afferent neurons are a critical component in prediabetes initiation, promoting islet inflammation through altered glucose homeostasis and progressive β cell stress. These factors orchestrate a catastrophic cascade culminating in insulin insufficiency mediated by an autoimmune‐prone host. This neuro‐immuno‐endocrinological triad explains diabetic inflammation as a consequence of local neuropeptide deficiency, leading to an innovative concept of disease pathogenesis with novel therapeutic implications.