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. 2021 Feb 5;12:805. doi: 10.1038/s41467-021-21133-3

Fig. 2. IL-22 from Th/Tc22 cells are required for induction of SR-Gut-aGVHD.

Fig. 2

ac Recipients were given 1-DEX, 4-DEX, or saline treatment as described in Fig. 1. Cytokine profiles of T cells from spleen and MLN were measured on day 25. Means ± SEM of % and yield of IL17A+IL-22, IL17A+IL-22+, and IL17AIL-22+ among CD4+ and CD8+ T subsets are shown in ac, respectively. Each dot represents one mouse. n = 4 (1-DEX), 6 (Saline), 7 (4-DEX) combined from two replicates. d Representative flow cytometry patterns and means ± SEM of AHR+RORγt and AHRRORγt+ among IL-17A+IL-22 or IL-17AIL-22+ CD4+ and CD8+ subsets. Each dot represents one mouse, n = 4, two replicates. e Means ± SEM of % and yield of IFN-γ+CD4+ and IFN-γ+CD8+ T in ileum. Each dot represents one mouse, n = 4, two replicates. f Recipients engrafted with splenic T from WT or IL-22−/− donors combined with TCD-BM from WT donors were given 4-DEX treatment. The recipients of WT-T were given additional treatment of anti-IL-22 mAb or IgG at 150 µg every 3 days from days 12 to 21 after HCT. On day 25, histopathology of colon was evaluated. Representative micrographs (200×) and %mice with indicated histopathological scores are shown; n = 4 (WT-IgG & IL-22−/− T), 12 (WT-anti-IL-22) biologically independent mice combined from two replicates. g, h Recipients engrafted with T cells from WT or T-RORγt−/− combined with TCD-BM from WT donors were evaluated for cytokine profile of MLN T cells and histopathology of colon on day 25. g Means ± SEM of % and yields of IL17AIL-22+ cells among CD4+ and CD8+ T-cell subsets; each dot represents one mouse, n = 5 (RORγt−/− T), 7 (WT T) combined from two replicates. h Representative micrographs of colon (200×) and %mice with indicated histopathological scores; n = 8 biologically independent mice combined from two replicates. P value was determined by two-way ANOVA with Tukey’s (ac) or Sidak’s (d), unpaired two-tailed Student’ t test (e, g). a ****p < 0.0001; yield of IL17A+IL-22CD4+: **p = 0.0013, ***p = 0.0004; yield of IL17A+IL-22CD8+: *p = 0.0416, **p = 0.0024 (spleen, saline vs 4-DEX),**p = 0.0074 (MLN, Saline vs 4-DEX); c ****p < 0.0001; yield of IL17AIL-22+CD4+: **p = 0.0024 (saline vs 4-DEX) **p = 0.0050 (1-DEX vs 4-DEX); %IL17AIL-22+CD8+: *p = 0.0256 (saline vs 1-DEX), *p = 0.0362 (1-DEX vs 4-DEX); ***p = 0.001,****p < 0.0001. Yield of IL17AIL-22+CD8+: ****p < 0.0001, **p = 0.0040, *p = 0.0493. d ****p < 0.0001. e *p = 0.0155, **p = 0.0032. g *p = 0.0410, ***p = 0.0003, ****p < 0.0001. Dexamethasone (DEX), MLN (mesenteric lymph node).