Regulated expression of nuclear receptor ROR t confers distinct functional fates to NK cell receptor-expressing ROR t(+) innate lymphocytes

Whether the recently identified innate lymphocyte population coexpressing natural killer cell receptors (NKRs) and the nuclear receptor ROR t is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. By using adoptive transfer of genetically tagged LTi-like cells, we demonstrate that NKR ? ROR t(+) innate lymphocytes but not NK cells were direct progenitors to NKR(+)ROR t(+) cells in vivo. Genetic lineage tracing revealed that the differentiation of LTi-like cells was characterized by the stable upregulation of NKRs and a progressive loss of ROR t expression. Whereas interleukin-7 (IL-7) and intestinal microbiota stabilized ROR t expression within such NKR-LTi cells, IL-12 and IL-15 accelerated ROR t loss. ROR t(+) NKR-LTi cells produced IL-22, whereas ROR t ? NKR-LTi cells released IFN- and were potent inducers of colitis. Thus, the ROR t gradient in NKR-LTi cells serves as a tunable rheostat for their functional program. Our data also define a previously unappreciated role of ROR t ? NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases.