Type I diabetes is autoimmune disease leading to destruction of insulin-secreting endocrine β islets in pancreas and glucose intolerance. NOD mouse strain represents well established model of human type I diabetes. So far, researchers identified several potential auto-antigens targeted by self-reactive T cells, out of which so far only mutation in insulin B chain (B:9–23) showed effect on disease progression.
Now, this Cutting Edge study in Journal Immunology showed that absence of another auto-antigen, Chromogranin A (ChgA), fully protected NOD mice from diabetes development.
First, the authors showed that β islets of NOD.ChgA-/- could not activate ChgA-specific T cell clones in an in vitro assay (reactivity to other auto-antigens insulin and IAPP was intact).
Importantly, the authors showed that NOD.ChgA-/- mice were completely protected from development of diabetes [measured as excess of glucose in urine samples].
Finally, the authors showed that NOD.ChgA-/- mice showed minimal β islets inflammation (insulitis) but developed comparable salivary gland inflammation (sialitis), implying that Chromogranin A effect was strictly β islets selective.
In summary, this study showed that at least Chromogranin A is necessary and sufficient for development of diabetes in NOD mice. Still, it is puzzling that NOD.ChgA-/- mice is protected from diabetes when they still expressed another dominant auto-antigen insulin [because earlier study showed that NOD ins1-/- ins2-/- mice were protected from diabetes development too]. If both auto-antigens are "priming epitopes" then both NOD.ChgA-/- and NOD ins1-/- ins2-/- mice should have developed diabetes. Strange.
David Usharauli
Finally, the authors showed that NOD.ChgA-/- mice showed minimal β islets inflammation (insulitis) but developed comparable salivary gland inflammation (sialitis), implying that Chromogranin A effect was strictly β islets selective.
In summary, this study showed that at least Chromogranin A is necessary and sufficient for development of diabetes in NOD mice. Still, it is puzzling that NOD.ChgA-/- mice is protected from diabetes when they still expressed another dominant auto-antigen insulin [because earlier study showed that NOD ins1-/- ins2-/- mice were protected from diabetes development too]. If both auto-antigens are "priming epitopes" then both NOD.ChgA-/- and NOD ins1-/- ins2-/- mice should have developed diabetes. Strange.
David Usharauli
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