Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells

The transcription factor ROR gamma t is required for the development of several innate lymphoid populations, such as lymphoid tissue-inducer cells (LTi cells) and cells that secrete interleukin 17 (IL-17) or IL-22. The progenitor cells as well as the developmental stages that lead to the emergence of ROR gamma t(+) innate lymphoid cells (ILCs) remain undefined. Here we identify the chemokine receptor CXCR6 as an additional marker of the development of ILCs and show that common lymphoid progenitors lost B cell and T cell potential as they successively acquired expression of the integrin alpha(4)beta(7) and CXCR6. Whereas fetal ROR gamma t(+) cells matured in the fetal liver environment, adult bone marrow-derived ROR gamma t(+) ILCs matured outside the bone marrow, in a Notch2-dependent manner. Therefore, fetal and adult environments influence the differentiation of ROR gamma t(+) cells differently.