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Innate lymphoid cells (ILCs) are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. Here, we show that NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP). Cell-intrinsic Nfil3 ablation led to variably impaired development of fetal and adult ILC subsets. Conditional gene targeting demonstrated that NFIL3 exerted its function prior to ILC subset commitment. Accordingly, NFIL3 ablation resulted in loss of ID2(+) CHILP and PLZF(+) ILC progenitors. Nfil3 expression in lymphoid progenitors was under the control of the mesenchyme-derived hematopoietin IL-7, and NFIL3 exerted its function via direct Id2 regulation in the CHILP. Moreover, ectopic Id2 expression in Nfil3-null precursors rescued defective ILC lineage development in vivo. Our data establish NFIL3 as a key regulator of common helper-like ILC progenitors as they emerge during early lymphopoiesis.

Original publication

DOI

10.1016/j.celrep.2015.02.057

Type

Journal article

Journal

Cell reports

Publication Date

19/03/2015

Volume

10

Pages

2043 - 2054

Addresses

Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France.

Keywords

Lymphocytes, Killer Cells, Natural, Animals, Mice, Inbred C57BL, Cell Differentiation, Lymphopoiesis, Cell Lineage, Basic-Leucine Zipper Transcription Factors, Lymphoid Progenitor Cells, Immunity, Innate