Figure 8.

MERTK signaling prevents rapid T1D progression in mice and MERTK-expressing cells are increased in the remaining insulin-containing islets of T1D patients. (A and B) NOD female mice >20 wk of age or WT C57BL/6 female mice were treated orally twice daily with 30 mg/kg UNC2025 or saline vehicle twice daily for 16 h (A) or 14 d (B). (A) Quantification of islet infiltration following MERTK inhibition. Whole pancreata were isolated and fixed before sectioning and staining. Sections were scored blindly for islet infiltration using the standard insulitis scale of 0 (uninfiltrated islet) to 4 (completely destroyed islet). n = 45 islets per condition from five or six mice per group from two independent experiments. Statistics: Student’s t test of islet scores. (B) Diabetes incidence with MERTK inhibition. Mice were monitored daily for blood glucose values. Mice with two consecutive blood glucose readings of >250 mg/dl were considered to be diabetic. n = 6–14 mice per group from four independent experiments. Statistics: Mantel–Cox test. (C–E) Immunofluorescent staining of pancreas sections from T1D patient and control donors. (C) Representative images of MERTK staining (green), CD68 staining (red), insulin staining (blue), and tissue autofluorescence (white). The dotted line indicates the islet border. Scale bars, 30 µm. (D) Donor information. (E) Blinded quantification of MERTK-expressing cell number per islet section. n = 118 islets from 9 T1D patients and 131 islets from 10 controls. Error bars represent SEM. Statistics: two-tailed Student’s t test. *, P < 0.05; **, P < 0.01; ****, P < 0.0001.