The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors [CUT&RUN]

Helper innate lymphoid cells (ILC) play important functions in immunity and tissue homeostasis, but their development remains poorly understood. In this study, we identified NFIL3 as the earliest known requirement during ILC development. Forced expression of NFIL3 in mouse lymphoid progenitors in vitro triggered the staged expression of downstream transcription factors including Tcf7, Gata3, Zbtb16 and Id2 that are implicated in ILC development. Thus, NFIL3 resides at the apex of a hierarchy of transcription factors important for innate lymphocyte development, and is necessary and sufficient to impose the innate lymphoid cell fate. Overall design: Cleavage Under Targets and Release Using Nuclease (CUT&RUN) in lymphoid precursors transduced to express NFIL3-HA for specific binding, or NFIL3 for control background with the anti-HA antibody