'Sensing' autoimmunity in type 1 diabetes

Trends Mol Med. 2007 Oct;13(10):405-13. doi: 10.1016/j.molmed.2007.07.006. Epub 2007 Sep 27.


Type 1 diabetes (T1D) results from autoimmune-mediated loss of insulin-producing beta-cells. Recent findings suggest that the events controlling T1D development are not only immunological, but also neuronal in nature. In the non-obese diabetic (NOD) mouse model of T1D, a mutant sensory neuron channel, TRPV1, initiates chronic, progressive beta-cell stress, inducing islet cell inflammation. This novel mechanism of organ-specific damage requires a permissive, autoimmune-prone host, but ascribes tissue specificity to the local secretory dysfunction of sensory afferent neurons. In NOD mice, normalizing this neuronal function by administration of the neurotransmitter substance P clears islet cell inflammation, reduces insulin resistance and restores normoglycemia. Here, we discuss this neuro-immuno-endocrine model, its implications and the involvement of sensory neurons in other autoimmune disorders. These developments might provide novel neuronal-based therapeutic interventions, particularly in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Humans
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Models, Biological
  • Neurons, Afferent / immunology
  • Neurons, Afferent / metabolism
  • Neurotransmitter Agents / metabolism


  • Neurotransmitter Agents