Non-invasive imaging of islet infiltration reveals an early window of CRIg-dependent diabetes determinism in NOD mice

Abstract All juvenile NOD mice exhibit insulitis, but there is substantial variation in progression to diabetes. We demonstrate that a patient-validated magnetic-resonance-imaging strategy to non-invasively visualize local effects of pancreatic-islet inflammation can predict diabetes onset in NOD mice. MRI signals acquired during a narrow early time-window allowed pre-sorting into disease-progressors and -nonprogressors and an estimate of time-to-diabetes. We exploited this capability to identify novel elements correlated with disease protection. Highlighted was CRIg (complement receptor of the immunoglobulin superfamily), which tagged a subset of macrophages associated with diabetes resistance. Administration of CRIg-Fc to young NODs depressed MRI signals and diabetes incidence. Besides nominating new regulators of disease progression, this study demonstrated that diabetes is set at an early age in NOD mice.