Extended Data Fig. 6: Cysteine-rich diet stimulates IL-22 production from crypt-associated CD8αβ⁺ T cells.

a, Relative fold change of selected, highly expressed cytokines in small-intestinal tissue after 6 weeks of CysRD feeding, as measured with the Mouse XL cytokine array (n = 3 per group). b, Representative images of Cxcl10 ISH staining in the crypts from control- and CysRD-fed mice. Scale bar, 20 µm. c, Fraction of intraepithelial CD8αβ⁺ T cells in control-IgG and CXCL10 neutralized cohorts (n = 5 per group). d, Flow cytometry for intraepithelial CD8αβ⁺ T cell gating panel (up), and anti-IL-22-PE histogram (down) in control- and CysRD-fed mice. e, IHC for HMGCS2 in the intestinal crypts from control and IL-22 i.p. injected mice. Scale bar, 20 µm. f, Flow cytometry for intraepithelial IL-22-GFP⁺ cell gating panel (left), and CD8β⁺ T cells histogram (right) in control- and CysRD-fed mice. g-j, Fraction of IL22-GFP⁺ immune cells in the IEL and LPL compartments of control- and CysRD-fed mice, assessed in both unirradiated (g, h) and irradiated (i, j) cohorts (n = 5 per group). k, Schematic of the CD8αβ⁺ T cells isolation, transplantation into Rag2^−/− mice, dietary regimen, and intestinal regeneration assay, including the timeline of diet treatment, irradiation (XRT, 7.5 Gy x 2) and tissue collection. l-m, Representative images and quantification of day-3 regenerating crypts stained with BrdU cell proliferation marker (l), and Lgr5 (ISH) (m) stem cell marker from 5 Rag2^−/−, 5 Rag2^−/− with CD8αβ^IL22-KO, and 5 Rag2^−/− with CD8αβ^IL22-WT mice intestine. Scale bar, 20 µm. Related to Fig. 3g–i. Unpaired two-tailed Student’s t-tests (c, g, i, l, m). Data (h, j) are mean ± s.d. Box and whiskers (c, g, i) are plotted min to the max value.

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