Figure 5. Pharmacological activation of GPR81 ameliorates mucosal inflammation.

(A-E) CD45RB^hiCD4⁺ T cells isolated from WT mice were adoptively transferred into Rag2^−/− mice. Animals were treated with GPR81 agonist orally (3-chloro-5-hydroxybenzoic acid (3Cl-5OH-BA); 10 mg/kg; on Weeks 1, 2, 3 and 4) and monitored over a period of time for percent weight loss compared to initial weight. (A) Percent weight change for Rag2^−/− mice treated with 3Cl-5OH-BA compared with untreated mice at various weeks post-naïve CD4⁺ T cell adoptive transfer. (B, C) Representative colon histology (H&E staining with original 10X magnification) and histology scores of Rag2^−/− mice 6 weeks post-naïve CD4⁺ T cell transfer treated with or without 3Cl-5OH-BA treatment. (D, E) Representative FACS plots and cumulative frequencies of colonic IL-17A⁺, IFN-γ⁺ and IL-10⁺ CD4⁺ T cells from Rag2^−/− mice treated with 3Cl-5OH-BA treatment compared with untreated mice on week 6 post-naïve CD4⁺ T cell adoptive transfer. (F) Excised colon samples in panel C were cultured for 2 days ex vivo, and then the secreted IL-17A, IFN-γ and IL-10 cytokine amounts in the culture supernatants were quantified by ELISA. Data are representative of three independent experiments (n>6). The error bars indicate mean ± SEM. **p<0.01; ***p<0.001.