Format

Send to

Choose Destination
Immunity. 2019 Apr 16;50(4):1054-1068.e3. doi: 10.1016/j.immuni.2019.02.022. Epub 2019 Mar 26.

An Id2RFP-Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials.

Author information

1
Innate Immunity Unit, Institut Pasteur, Paris 75724, France; Inserm U1223, Institut Pasteur, Paris 75724, France; Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: wei_xuxx@fudan.edu.cn.
2
Innate Immunity Unit, Institut Pasteur, Paris 75724, France; Inserm U1223, Institut Pasteur, Paris 75724, France; Paris Diderot University, Sorbonne Paris Cité, Paris 75013, France.
3
Inserm U1223, Institut Pasteur, Paris 75724, France; Lymphopoiesis Unit, Institut Pasteur, Paris 75724, France.
4
Innate Immunity Unit, Institut Pasteur, Paris 75724, France; Inserm U1223, Institut Pasteur, Paris 75724, France.
5
Inserm U1223, Institut Pasteur, Paris 75724, France; Paris Diderot University, Sorbonne Paris Cité, Paris 75013, France; Lymphopoiesis Unit, Institut Pasteur, Paris 75724, France.
6
Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
7
Innate Immunity Unit, Institut Pasteur, Paris 75724, France; Inserm U1223, Institut Pasteur, Paris 75724, France. Electronic address: james.di-santo@pasteur.fr.

Abstract

Innate lymphoid cell (ILC) development proposes that ILC precursors (ILCPs) segregate along natural killer (NK) cell versus helper cell (ILC1, ILC2, ILC3) pathways, the latter depending on expression of Id2, Zbtb16, and Gata3. We have developed an Id2-reporter strain expressing red fluorescent protein (RFP) in the context of normal Id2 expression to re-examine ILCP phenotype and function. We show that bone-marrow ILCPs were heterogeneous and harbored extensive NK-cell potential in vivo and in vitro. By multiplexing Id2RFP with Zbtb16CreGFP and Bcl11btdTomato strains, we made a single-cell dissection of the ILCP compartment. In contrast with the current model, we have demonstrated that Id2+Zbtb16+ ILCPs included multi-potent ILCPs that retained NK-cell potential. Late-stage ILC2P and ILC3P compartments could be defined by differential Zbtb16 and Bcl11b expression. We suggest a revised model for ILC differentiation that redefines the cell-fate potential of helper-ILC-restricted Zbtb16+ ILCPs.

KEYWORDS:

cell fate; differentiation; innate immunity; lymphocyte; transcription factor

PMID:
30926235
PMCID:
PMC6477155
DOI:
10.1016/j.immuni.2019.02.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center