Fig 2: Epithelial-derived IL-33 signaling expands colonic ST2+ regulatory T (Treg) cells and induces a Th2 cytokine profile. (A) Relative and absolute number of Treg cells (CD4+Foxp3+) in the colon of Apc Min/+ mice and V33 Apc Min/+ mice at d120. Left, representative flow cytometry plots gated on CD45+ cells; right, statistical data show means ± s.e.m. (B) Relative and absolute number of ST2+ Treg cells in the colon of Apc Min/+ mice and V33 Apc Min/+ mice at d120. Left, representative flow cytometry plots gated on CD45+ CD4+ cells; right, statistical data show means ± s.e.m. (C) Relative expression levels of ST2+Treg and Th2 signature genes were analyzed by qPCR in sorted T cells of colonic lamina propria of WT, V33, Apc Min/+ mice and V33 Apc Min/+ mice at d120. Graphs show means ± s.e.m., n = 4–5/group. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA.

Fig 3: Schematic representation of the role of IL-33 and miR-29a in tendon pathology.Tendon injuries or repetitive micro tears causing stress of tendon cells result in the release of IL-33 from tenocytes or immune cells and the downstream phosphorylation of NFκB which in turn represses miR-29a causing an increase in collagen type 3 and sST2 production. IL-33 may also increase collagen synthesis in an ERK-dependent manner. The increased presence of collagen 3 reduces the tendon tensile strength lending to early tendon failure. However, elevated sST2 may act, in a feedback loop fashion, as a protective mechanism by removing excess IL-33 from the system.

Fig 4: Expression of interleukin (IL)-33 in the nasal mucosa. The panels show immunohistochemical findings for IL-33 (×400). Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). PBS, phosphate buffered saline; HPF, high-power field.

Fig 5: Genetic and/or pharmacological inhibition of the IL-33/ST2 axis reduced colonic inflammation in a chemical-induced model of acute colitis. (A) Disease activity index (DAI), (B) Histological Score, (C) IL-6 and (D) KC ELISA from colon homogenates and (E) Colon length of dextran sodium sulphate (DSS)-treated wild-type and St2−/− animals. Mean values of DAI±SEM out of four independent experiments are shown. (F) DAI (G) Histological Score, (H) IL-6 ELISA from colon homogenates of DSS-treated mice administered 50 µg neutralising anti-ST2 antibody (rat IgG1) or isotype control intraperitoneally on days 1, 3, 5 and 7. (I) Histological Score and (J) Colon length of DSS-treated wild-type and IL-33-deficient mice. Mean values of four animals per group±SEM out of two independent experiments.