In addition to the blockade of IL-21 by IL-21R.Fc neutralization, we further explored the effects of genetic disruption of IL-21 signaling on Blimp-1 deficiency–mediated colitis by crossing IL-21R–deficient mice with Blimp-1 CKO mice to generate a double-knockout (DKO) mouse model. The gene discussed is IL21; the disease is colitis.