Inhibition of host AHR activation exacerbates IPS. (A-B) B6 mice that received TCD BM cells, and T cells of BALB/c mice were intraperitoneally injected with CH-223191 (10 mg/kg) every day from day 3 through day 8. Lungs were harvested on day 9. (A) Ido1, Ahr, and Cyp1b1 expression were measured by real-time polymerase chain reaction (PCR). (B) Cyp1b1 expression was measured in isolated CD4⁺ T cells and lung epithelial cells by real-time PCR. (C-G) B6.WT or B6.Ahr^−/− mice received TCD BM cells and T cells of BALB/c mice. Lungs were harvested on day 9. (C) Cyp1b1 expression was measured in isolated CD90⁺ T cells and CD90⁻ non-T cells of B6.Ahr^−/− mice by real-time PCR. (D) Representative images (×200; left) and histopathologic scoring (right). (E) Levels of cytokine messenger RNA (mRNA) were measured in whole lungs by real-time PCR. (F-G) Single-cell suspensions of lung tissue were stimulated with anti-CD3/CD28 for 3 hours for fluorescence-activated cell sorting analysis or 24 hours for harvesting culture supernatant (n = 5 per group). (F) Staining of CD4 and IL-17A or FoxP3 were performed, and ratio of IL-17A⁺/FoxP3⁺ CD4⁺ T cells was obtained (n = 5 per group). (G) Concentrations of IL-17A and IL-10 were measured in culture supernatant. (H-I) Mixed chimeric mice were generated by transplanting B6.WT or B6.Ahr^−/− BM into lethally irradiated B6.WT or B6.Ahr^−/− mice. After 2 months, the chimeric mice received TCD BM cells and T cells of BALB/c mice. Lungs were harvested on day 9 (n = 5 per group). (H) Representative images (200×; left) and histopathologic scoring (right). (I) Levels of cytokine mRNA were measured by real-time PCR. Results are representative of 2 (B-C,H-I) or 3 independent experiments with similar results. Data represent mean ± standard error of the mean. Nonparametric Mann-Whitney U test (A-G) and 1-way analysis of variance (H-I) were performed. *P < .05, **P < .01, ***P < .001.