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

摘要

Whether the recently identified innate lymphocyte population coexpressing natural killer cell receptors (NKRs) and the nuclear receptor RORgammat 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 NKRRORgammat(+) innate lymphocytes but not NK cells were direct progenitors to NKR(+)RORgammat(+) 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 RORgammat expression. Whereas interleukin-7 (IL-7) and intestinal microbiota stabilized RORgammat expression within such NKR-LTi cells, IL-12 and IL-15 accelerated RORgammat loss. RORgammat(+) NKR-LTi cells produced IL-22, whereas RORgammat NKR-LTi cells released IFN-gamma and were potent inducers of colitis. Thus, the RORgammat gradient in NKR-LTi cells serves as a tunable rheostat for their functional program. Our data also define a previously unappreciated role of RORgammat NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases.