Extended Data Fig. 3: Overexpression of IL-15 in HLA-humanized DQ8 mice confers susceptibility to development of coeliac disease-like features in a gluten-dependent manner.

a–k, DQ8 and DQ8-D^d-villin-IL-15tg mice were maintained on a GFD or fed gluten for 30 days. a, Left, H&E staining of paraffin-embedded ileum sections. Scale bars, 100 µm. Right, the ratio of the morphometric assessment of villus height to crypt depth (DQ8 sham, n = 12, gluten n = 13; DQ8-D^d-villin-IL-15tg sham, n = 12, gluten n = 15). b, Villus/crypt ratio from sham-fed DQ8-D^d-villin-IL-15tg mice and DQ8-D^d-villin-IL-15tg mice fed a standard rodent chow without supplementary gluten (sham, n = 4, gluten n = 8). c, IgA (red) and CD138⁺ (green) plasma cells were distinguished by immunohistochemical staining of frozen ileum sections. Scale bars, 50 μm. d, Serum levels of anti-DGP IgG as measured by ELISA. Serum was collected 30 days after gluten feeding (DQ8 sham, n = 6, gluten n = 7; DQ8-D^d-villin-IL-15tg sham, n = 6, gluten n = 7). e, Quantification of IELs among IECs performed on H&E-stained ileum sections (DQ8 sham, n = 10, gluten n = 16; DQ8-D^d-villin-IL-15tg sham, n = 12, gluten n = 14). f–j, The intestinal epithelium was isolated and analysed by flow cytometry. IELs were identified as TCRβ⁺CD4⁻CD8⁺ and TCRβ⁺CD4⁻CD8αβ⁺ cells. f, Percentage of granzyme B⁺ IELs (DQ8 sham, n = 13, gluten n = 15; DQ8-D^d-villin-IL-15tg sham, n = 11, gluten n = 15). g, Numbers of CD8⁺ granzyme B⁺ IELs per 100 IECs (DQ8 sham, n = 11, gluten n = 14; DQ8-D^d-villin-IL-15tg sham, n = 11, gluten n = 13). h, MFI of granzyme B (DQ8 sham, n = 11, gluten n = 12; DQ8-D^d-villin-IL-15tg sham, n = 9, gluten n = 12). i, Percentage of NKG2D⁺NKG2⁻ IELs (DQ8 sham, n = 13, gluten n = 17; DQ8-D^d-villin-IL-15tg sham, n = 11, gluten n = 15). j, Numbers of NKG2D⁺NKG2⁻ IELs per 100 IECs (DQ8 sham, n = 12, gluten n = 16; DQ8-D^d-villin-IL-15tg sham, n = 11, gluten n = 13). k, The intestinal epithelium was isolated and analysed by flow cytometry. IECs were identified as EpCAM⁺CD45⁻ cells. Percentage of Rae-1⁺ IECs (n = 5 mice per group). Data are mean values (a, b, d–k) from four (a, e–g, i, j), two (b, d, k) or three (c, h) independent experiments. P values were determined by one-way ANOVA with Tukey’s multiple comparison test (a, d–k) or unpaired, two-tailed, t-test (b).

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