Fig 2: Effector T cells of DRA KO mice colonic lamina propria exhibited a type 2 phenotype. Isolated colonic lamina propria lymphocytes were gated for CD4+ and TCRß+ effector T cells (Th), followed by various subtypes using fluorescence assisted cell sorting (FACS). (A) Gating strategy used for CD4+ T cells. (B) Dot plot shows CD4+ and GATA3+ double positive Th2 in WT vs DRA KO mice. (C) Histogram show 3 peaks for GATA3 in WT (black) and DRA KO mice (green). Bar diagram shows (D) percentage and (E) total number of GATA3+ effector T cells in WT and DRA KO mice. (F) Representative dot plot shows ROR?t+ Th17 (lower right quadrant, labeled in blue) and FOXP3+ Tregs (upper left quadrant, labeled in magenta) in WT and DRA KO mice. Bar graph shows (G) percentage and (H) total number of ROR?t+ Th17 cells. Bar diagram represents (I) percentage and (J) total number of FOXP3+ Tregs in WT and DRA KO mice. (K) Representative dot plot shows ROR?t+ and FOXP3+ populations. Bar diagram shows (L) percentage and (M) total number of ROR?t+ and FOXP3+ iTregs in WT vs DRA KO mice. (N) Representative dot plot for FOXP3+ and GATA3+ iTregs. Bar diagram shows (O) percentage and (P) total number of GATA3+ and FOXP3+ iTregs. Data are presented as mean ± standard error of mean, n = 6–7. *P < .05, **P < .005, ***P < .0005 vs WT.

Fig 3: Neutralization of IL-33 via anti-IL-33 antibody in DRA KO mice alleviated the elevated type 2 lymphocyte phenotype. Mouse anti-IL-33 antibody (1 mg/mouse/day) was administered to WT and DRA KO mice for 7 days by intraperitoneal injections, and colonic lamina propria cells were harvested and gated as before for various immune cell phenotypes. (A) Representative dot plots for KLRG+ ILCs. (B) Bar diagram shows percentage of ILC2s after anti-IL-33 administration in WT vs DRA KO mice. (C) Bar diagram shows IL-13+ ILC2s in WT and DRA KO mice after anti-IL-33 treatment. (D) Representative dot plots depict GATA3 and FOXP3 positive CD4+ T cells in WT and DRA KO mice after anti-IL-33 administration. (E) Bar graph for GATA3+ Th2 in WT vs DRA KO mice. (F) Cartoon shows conversion of CD4+ T cells to mucosal tissue resident GATA3+ and FOXP3+ iTregs driven by IL-33. (G) Bar diagram for GATA3+ and FOXP3+ iTregs after anti-IL-33 treatment. Data are presented as mean ± standard error of mean, n = 4. *P < .05, **P < .005, ***P < .0005. (Groups: WT, WT IgG; WT anti IL-33; DRA KO, DRA KO IgG; DRA KO anti-IL-33).

Fig 4: iNKT cells frequency and cell subsets in PBMCs of psoriasis patients. (A) Representative FACS dot plots for iNKT cells from psoriasis patients and healthy controls. (B) Summary plots showing individual results of iNKT cell frequency in psoriasis patients versus healthy controls. (C) Representative FACS dot plots for iNKT cell CD4 expression in psoriasis patients and healthy controls. (D) Summary plots showing individual results of the frequency of CD4+ iNKT cells in psoriasis patients versus healthy controls. (E) Representative histogram and summary plots showing individual results of the MFI for T-bet + iNKT cells in psoriasis patients and healthy controls. (F) Representative histogram and summary plots showing individual results of the MFI for GATA3+ iNKT cells in psoriasis patients and healthy controls. (G) Representative histogram and summary plots showing individual results of the MFI for ROR?t + iNKT cells in psoriasis patients and healthy controls. (H) Summary plots showing individual results of GATA3+ iNKT cells/ROR?t + iNKT cells, ROR?t + iNKT cells/T-bet + iNKT cells and GATA3+ iNKT cells//T-bet + iNKT cells in psoriasis patients versus healthy controls. Data show mean +SEM. p-values were determined by paired Student’s t-test. ns, no significance, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.

Fig 5: Increased frequency of iNKT cells in psoriasis patients treated with secukinumab. PBMC were isolated from psoriasis patients (n = 15) at baseline untreated (Week 0) and 12 Weeks post treatment with secukinumab. (A) Representative FACS dot plots for iNKT cells from psoriasis patients before and after secukinumab treatment versus healthy controls. (B) Summary plots showing individual results of iNKT cell frequency in psoriasis patients before and after secukinumab treatment. (C) Summary plots showing individual results of T-bet+ iNKT cells frequency in psoriasis patients before and after secukinumab treatment. (D) Summary plots showing individual results of GATA3+ iNKT cells frequency in psoriasis patients before and after secukinumab treatment. (E) Summary plots showing individual results ROR?t+ iNKT cells frequency in psoriasis patients before and after secukinumab treatment. Data show mean +SEM. p-values were determined by paired Student’s t-test. ns, no significance, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.