Immunity
Volume 50, Issue 4, 16 April 2019, Pages 1054-1068.e3
Journal home page for Immunity

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

https://doi.org/10.1016/j.immuni.2019.02.022Get rights and content
Under a Creative Commons license
open access

Highlights

  • A highly sensitive Id2-reporter strain allows identification of ILC precursors

  • Id2+ ILCPs harbor multi-potent NK and/or ILC precursors at the clonal level

  • Id2+Zbtb16+ ILCPs retain substantial conventional NK-cell potential

Summary

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

lymphocyte
cell fate
differentiation
transcription factor
innate immunity

Cited by (0)

7

These authors contributed equally

8

Lead Contact