LAUSR

Innate lymphoid cells (ILCs), composed of heterogeneous populations of lymphoid cells, contribute critically to immune surveillance at mucosal surfaces. ILC subsets develop from common lymphoid progenitors through stepwise lineage specification. However, the composition and temporal regulation of the transcription factor network governing such a process remain incompletely understood. Here we report that deletion of the transcription factor interferon regulatory factor 2 (IRF-2), known also for its importance in conventional NK cell maturation, resulted in an impaired generation of ILC1, ILC2 and ILC3 subsets with lymphoid tissue inducer-like (LTi) cells hardly affected. In IRF-2-deficient mice, PD-1hi ILC precursors (ILCPs) that generate these three ILCs but not LTi cells were present at normal frequency, while their subpopulation expressing high amounts of PLZF, another marker for ILCPs, was severely reduced. Notably, these IRF-2-deficient ILCPs contained normal quantities of PLZF-encoding Zbtb16 messages, and PLZF expression in developing invariant NKT cells within the thymus was unaffected in these mutant mice. These results point to a unique, cell-type selective role for IRF-2 in ILC development, acting at a discrete step critical for the generation of functionally competent ILCPs.