'Sensing' autoimmunity in type 1 diabetes.
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.
Tsui
Hubert
H
The Hospital for Sick Children, Department of Neuroscience and Mental Health, 555 University Avenue, 10128 Elm Wing Toronto, ON, M5G 1X8, Canada.
Razavi
Rozita
R
Chan
Yin
Y
Yantha
Jason
J
Dosch
H-Michael
HM
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008954:Models, Biological; D009475:Neurons, Afferent / Q000276:immunology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism
D018377:Neurotransmitter Agents