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Updated: Jan 12, 2026

Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors
Joseph Léger1, Eva Artano1, Delphine Coulais1
1Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, 44007 Nantes, France.
None:
Understanding the mechanisms that initiate innate lymphoid cell (ILC) specification may reveal how ILC functions in immunity and tissue homeostasis are programmed. Using an Il7r-lineage tracing mouse strain, we identified developmental intermediates between lymphoid progenitors and Tcf7+ ILC progenitors in the mouse bone marrow (BM). Transcriptional analysis of these intermediates identified very early expression of the transcription factor nuclear factor, interleukin 3 regulated (NFIL3). Nfil3-/- mice lacked all BM ILC-specified precursors. Forced expression of NFIL3 in lymphoid progenitors induced Tcf7+ ILC-lineage cells capable of generating all ILC subsets and conventional natural killer cells. Transient activity of NFIL3 in lymphoid precursors recapitulated BM ILC development in vitro, leading to the generation of all adult ILCs. Mechanistically, NFIL3 initiated ILC specification by inducing expression of key transcriptional regulators of ILC development-Tox, Id2, Gata3, Tcf7, and Zbtb16. Our findings indicate an apex role for NFIL3 in ILC specification and provide an in vitro approach to generate ILC-lineage cells with potential therapeutic utility.
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