Figure 7. LUBAC is required for peripheral Treg cell homeostasis and tolerance.

(a) Kaplan–Meyer survival curve measured from birth to 60 days for mice of the indicated genotypes (P<0.0001 using the log-ranked Mantel–Cox test). (b) Weights of 18–22-day-old male and female Hoip^ΔFoxp3 mice and healthy littermate controls. (c) Runted appearance and (d) lymphadenopathy observed in Hoip^ΔFoxp3 mice, with mean cell number indicated. (e) Representative hematoxylin and eosin (haematoxylin and eosin) stained sections of lung, liver and pancreas of 21-day-old mice of the indicated genotypes (scale bars, 500 μm). (f) Plasma IgE concentrations in 18–22-day-old Hoip^ΔFoxp3 mice and healthy littermate controls. (g) Expression of CD44 and CD62L on CD4⁺FOXP3⁻ (top panel) and CD8⁺ T cells (bottom panel) in spleens of WT and Hoip^ΔFoxp3 mice. (h) Absolute numbers of CD44^highCD62L^low activated cells in the CD4⁺FOXP3⁻ and CD8⁺ population of WT and Hoip^ΔFoxp3 mice. (i) Representative flow cytometry plots and absolute numbers of FOXP3⁺TCRβ⁺ cells in the thymus (top panel), spleen (middle panel) and lymph nodes (bottom panel) of WT and Hoip^ΔFoxp3 mice. (j) Expression of Ki-67, CTLA-4, CD62L and BCL-2 in CD4⁺FOXP3⁺ cells in the spleen from WT (grey shaded histogram) and Sharpin^cpdm (black thick histogram) mice. Shpn^cpdm refers to Sharpin^cpdm mice. (n=6–9 per /genotype, bar graphs show mean±s.d.). *P<0.05, **P<0.01, ***P<0.005 and ****P<0.001, respectively. One-way analysis of variance with a Tukey's post-hoc test for multiple comparisons was used for statistical analysis. Data are pooled from (a,b,f,g,h) or representative (c–e) of three independent experiments with one to three mice per group.