Journal
BIOLOGY DIRECT
Volume 2, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1745-6150-2-5
Keywords
-
Categories
Funding
- NIDDK NIH HHS [R01 DK054063, P01 DK057644] Funding Source: Medline
Ask authors/readers for more resources
: Type 1 diabetes occurs when self-reactive T lymphocytes destroy the insulin-producing islet beta cells of the pancreas. The defects causing this disease have often been assumed to occur exclusively in the immune system. We present evidence that genetic variation at the Idd9 diabetes susceptibility locus determines the resilience of the targets of autoimmunity, the islets, to destruction. Susceptible islets exhibit hyper-responsiveness to inflammatory cytokines resulting in enhanced cell death and increased expression of the death receptor Fas. Fas upregulation in beta cells is mediated by TNFR2, and colocalization of TNFR2 with the adaptor TRAF2 in NOD beta cells is altered. TNFR2 lies within the candidate Idd9 interval and the diabetes-associated variant contains a mutation adjacent to the TRAF2 binding site. A component of diabetes susceptibility may therefore be determined by the target of the autoimmune response, and protective TNFR2 signaling in islets inhibit early cytokine-induced damage required for the development of destructive autoimmunity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available