Schistosoma-exposed IL-4−/−IL-13−/− mice have decreased phospho–signal transducer and activator of transcription factor 6 (STAT6), and STAT6 inhibition prevents Schistosoma-pulmonary hypertension. (A) Representative images showing representative immunostaining for phospho-Y641-STAT6 in Schistosoma-exposed wild-type (WT), IL-4−/−, IL-13−/−, and IL-4−/−IL-13−/− mice (images representative of n = 4/group; asterisks, vessel lumens; arrows, representative positive stained cells; scale bars, 50 μm). (B) Quantification of area staining positive for phospho-STAT6 in the pulmonary vascular adventitia in Schistosoma-exposed WT, IL-4−/−, IL-13−/−, and IL-4−/−IL-13−/− mice (mean ± SD; n = 4 specimens per group; analysis of variance, P = 0.009; post hoc Tukey test, ***P < 0.005). (C–E) IP/IV egg–exposed WT mice treated with the STAT6 inhibitor AS1517499 or equivalent volume of vehicle: right ventricular systolic pressure (RVSP) (mean ± SD; n = 7 mice per group; t test *P < 0.05) (C); granuloma volume (mean ± SD; n = 7 mice per group; t test *P < 0.05) (D); and quantitative fractional thickness of the pulmonary vascular media (mean ± SD; n = 7 mice per group; t test *P < 0.05) (E). α-SMA = α-smooth muscle actin; DAPI = 4′,6-diamidino-2-phenylindole; IP/IV = intraperitoneal and intravenous; RV = right ventricle.