NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors

Wei Xu (1) , Rita G. Domingues (2) , Diogo Fonseca-Pereira (2) , Manuela Ferreira (2) , Helder Ribeiro (2) , Silvia Lopez-Lastra (1) , Yasutaka Motomura (3) , Lara Moreira-Santos (2) , Franck Bihl (4) , Veronique Braud (4) , Barbara Kee (5) , Hugh Brady (6) , Mark C. Coles (7) , Christian A. J. Vosshenrich (1) , Masato Kubo (3) , James P. Di Santo (1) , Henrique Veiga-Fernandes (2)

1 Immunité Innée - Innate Immunity
2 iMM - Instituto de Medicina Molecular
3 RIKEN - RIKEN - Institute of Physical and Chemical Research [Japon]
4 IPMC - Institut de pharmacologie moléculaire et cellulaire
5 University of Chicago
6 Imperial College London
7 University of York [York, UK]

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.

Domains: Immunology

Wei Xu, Rita G. Domingues, Diogo Fonseca-Pereira, Manuela Ferreira, Helder Ribeiro, et al.. NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors. Cell Reports, 2015, 10, pp.2043-2054. ⟨10.1016/j.celrep.2015.02.057⟩. ⟨pasteur-01138721⟩