REG4/Reg4 can potentially be through multiple mechanisms to regulate sensitivity to DSS mediated colitis, such as gut cell development, gut immune cells and alteration of gut microbiota.38 Since we previously found REG4/Reg4 might cause increased IL-35+ immune cells through changed gut microbiota,39 we analyzed these IL-35+ cells in the CLP. The gene discussed is REG4; the disease is colitis.