Th1 and Th17 cells were significantly decreased and Th2 cells were notably increased in the spleen, but not in MLNs, of IL-21R.Fc–treated CKO mice, whereas there was no difference in Treg cells between treated and control groups in both spleens and MLNs (Figure 4D and Supplemental Figure 3A), suggesting that IL-21 blockade–mediated alleviation of colitis is through a systemic downregulation of pathogenic Th1 and Th17 cells and a boost in the protective Th2 subpopulation. The gene discussed is IL21; the disease is colitis.