Fig. 7. Lack of TGF-β signaling in γδ IELs exacerbates DSS-induced colitis.

a The volcano plot shows the differential expression profile of genes in TCRγδ⁺CD8αα⁺ IELs from R1 WT and R1 KO mice and examined by RNA-seq. The gray dots represent non-differentially expressed genes between the two groups, while the upregulated genes in R1 KO mice are pink dots towards the upper end (with log₂ fold change value above 0 on the y-axis), and the downregulated genes in R1 KO mice are pink dots towards the lower end (with log₂ fold change value below 0 on the y-axis). b FISH visualizes the location of bacteria around the intestinal epithelia in the small intestine of Smad3^−/− mice and age-matched littermate controls (Smad3^+/+). c FISH visualizes the location of bacteria in the small intestine from 5-day-tamoxifen-treated Tgfbr1^f/f TCRδ ER Cre and age-matched Tgfbr1^+/+ TCRδ ER Cre littermates. d, e DAI (d) and loss of body weight (e) of Smad3^−/− and Smad3^+/+ mice treated with 3% DSS drinking water for 7 days. f, g DAI (f) and loss of body weight (g) of Tgfbr1^f/f TCRδ ER Cre and Tgfbr1^+/+ TCRδ ER Cre control mice treated with DSS for 7 days. h–j Hematoxylin and eosin (H&E) staining for colon from normal Smad3^−/− and 5-day-tamoxifen-treated Tgfbr1^+/+f TCRδ ER Cre mice (h), and from 3% DSS-treated Smad3^−/− vs Smad3^+/+ mice in d and e (i), or 3% DSS-treated Tgfbr1^f/f TCRδ ER Cre versus Tgfbr1^+/+ TCRδ ER Cre mice in f and g (j). *P < 0.05 (unpaired two-tailed Student’s t-test or DEseq2 statistical test). Data were representative of at least two independent experiments (means ± SEM). RNA-seq samples were collected from three or four independent experiments.