title: NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors.
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.
authors: Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France.
authors: Wei
authors: W
authors: Xu
authors: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors: Rita G
authors: RG
authors: Domingues
authors: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors: Diogo
authors: D
authors: Fonseca-Pereira
authors: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors: Manuela
authors: M
authors: Ferreira
authors: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors: Hélder
authors: H
authors: Ribeiro
authors: Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France.
authors: Silvia
authors: S
authors: Lopez-Lastra
authors: 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.
authors: Yasutaka
authors: Y
authors: Motomura
authors: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
authors: Lara
authors: L
authors: Moreira-Santos
authors: Centre National de la Recherche Scientifique - UMR 7275 Institut de Pharmacologie Moléculaire et Cellulaire, 660 Route des Luciole, 06560 Valbonne, France.
authors: Franck
authors: F
authors: Bihl
authors: Centre National de la Recherche Scientifique - UMR 7275 Institut de Pharmacologie Moléculaire et Cellulaire, 660 Route des Luciole, 06560 Valbonne, France.
authors: Véronique
authors: V
authors: Braud
authors: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Barbara
authors: B
authors: Kee
authors: Department of Life Sciences, Imperial College, London SW7 2AZ, UK.
authors: Hugh
authors: H
authors: Brady
authors: Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York YO10 5DD, UK.
authors: Mark C
authors: MC
authors: Coles
authors: Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France.
authors: Christian
authors: C
authors: Vosshenrich
authors: 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.
authors: Masato
authors: M
authors: Kubo
authors: Innate Immunity Unit, Inserm U668, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France. Electronic address: james.di-santo@pasteur.fr.
authors: James P
authors: JP
authors: Di Santo
authors: 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.
authors: Henrique
authors: H
authors: Veiga-Fernandes
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000166:cytology*; D038041:Lymphopoiesis / Q000276:immunology*; D008810:Mice, Inbred C57BL
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse