Retinoid-related orphan receptor (ROR) gamma t-expressing and IL-22-producing NKp46(+) innate lymphoid (ILC22) cells reside in the lamina propria of the intestine in mice, suggesting that ILC22 cells contribute to host defense during intestinal damage in models of colitis in mice. Nevertheless, another set of pathological interferon (IFN)-gamma and/or IL-17A-producing innate lymphoid cells (ILC1 and ICL17) may participate in the pathogenesis in different models of colitis. We here showed that ROR gamma t(+)IL-22(+) ILC22 cells were localized in Thy-1(high)SCA-1(high) and/or Thy-1(high)SCA-1(low) subpopulations of the intestine in normal and dextran sodium sulfate (DSS)-induced colitic ROR gamma t-sufficient Rag-2(-/-) mice. ROR gamma t-deficient Rag2(-/-) mice developed more severe DSS-induced colitis accompanied with lower expression of REG3 beta and REG3 gamma in the colon, but with a lower ratio and absolute number of IFN-gamma-producing ILC1 cells as compared to control ROR gamma t-sufficient Rag-2(-/-) mice. Collectively, not only the presence of ILC22 cells but also the balance of protective and pathogenic ILCs may be involved in the prevention of colitis. (C) 2012 Elsevier Inc. All rights reserved.