Figure 8. Constitutively active IL-15 signaling in granzyme C-expressing ILC1s causes perforin-dependent lethal autoimmunity.

A. Granzyme C (GzmC) expression in liver (Liv) and salivary gland (SG) CD3⁻NK1.1⁺NKp46⁺ cells of wild-type (WT) and Il15^−/− mice. B. Experimental design of Gzmc^Stat5b-CA mice. C. Kaplan-Meier survival curves for Gzmc^Stat5b-CA/+, Gzmc^Stat5b-CA/+Rag1^−/−, and littermate control mice. D. GzmC⁺NK1.1⁺NKp46⁺ cells per gram of Liv tissue from seven-day-old WT and Gzmc^Stat5b-CA/+ mice. E. Representative images of hematoxylin and eosin staining (H&E, first row) and NKp46 (second row) and cleaved caspase 3 (CC3, third row) immunoreactivities (indicated by arrows) of Liv sections from 14-day-old WT, Gzmc^Stat5b-CA/+, and Gzmc^Stat5b-CA/+Prf1^−/− mice. Images and inserts are 200X and 400X, respectively. NKp46 and CC3 immunoreactivity was also quantified on serial sections as percent of total tissue using digital pathology software (Halo). Scale bar indicates 100 μm. F. Kaplan-Meier survival curves for Gzmc^Stat5b-CA/+ and Gzmc^Stat5b-CA/+Prf1^−/− littermate control mice (n = 15–18 per group). Each dot represents one mouse; A, D, E: n = 3–4 mice per group, C: n = 7–18 per group, F: n = 15–18 mice per group. All data are combined from three or more independent experiments and shown as mean +/− SEM (A, D, E: one-way ANOVA with Tukey’s multiple comparisons test, C, F: Log-rank [Mantel Cox] test; “ns” = not significant, * = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001)