Get access

Islet Glia, Neurons, and β Cells

The Neuroimmune Interface in the Pathogenesis of  Type 1 Diabetes

Authors

  • Hubert Tsui,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Shawn Winer,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Yin Chan,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Dorothy Truong,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Lan Tang,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Jason Yantha,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Geoffrey Paltser,

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Hans-Michael Dosch

    1. The Hospital for Sick Children, Research Institute, Departments of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author

Address for correspondence: Hans-Michael Dosch, M.D., Ph.D., The Hospital for Sick Children, Research Institute, 555 University Ave., Toronto, ON, Canada, M5G 1X8. Voice: 416-813-6260; fax: 416-813-6255. hmdosch@sickkids.ca

Abstract

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.

Ancillary