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Cell Rep. 2015 Mar 31;10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057. Epub 2015 Mar 19.

NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors.

Author information

1
Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France.
2
Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
3
Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
4
Centre National de la Recherche Scientifique - UMR 7275 Institut de Pharmacologie Moléculaire et Cellulaire, 660 Route des Luciole, 06560 Valbonne, France.
5
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
6
Department of Life Sciences, Imperial College, London SW7 2AZ, UK.
7
Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York YO10 5DD, UK.
8
Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi, Yokohama, Kanagawa 230-0045, Japan; Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba 278-0022, Japan.
9
Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France. Electronic address: james.di-santo@pasteur.fr.
10
Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal. Electronic address: jhfernandes@medicina.ulisboa.pt.

Abstract

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.

PMID:
25801035
DOI:
10.1016/j.celrep.2015.02.057
[Indexed for MEDLINE]
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