REG4 and inflammatory bowel disease: Results showed that rmIL-35 administration could indeed reduce the sensitivity of Reg4 KO mice to DSS-mediated colitis, whereas IL-35 neutralizing antibodies could increase sensitivity in huREG4IECtg mice (Figure 2e–I, Figure S5), consistent with the data that IL-35 reverses inflammatory bowel disease.40 Thus, our data clearly indicate that REG4/Reg4 mediated resistance to DSS-mediated colitis is dependent on IL-35.