TY - JOUR
T1 - KLRG1 and NKp46 discriminate subpopulations of human CD117+CRTH2- ILCs biased toward ILC2 or ILC3
AU - Nagasawa, Maho
AU - Heesters, Balthasar A.
AU - Kradolfer, Chantal M. A.
AU - Krabbendam, Lisette
AU - Martinez-Gonzalez, Itziar
AU - de Bruijn, Marjolein J. W.
AU - Golebski, Korneliusz
AU - Hendriks, Rudi W.
AU - Stadhouders, Ralph
AU - Spits, Hergen
AU - Bal, Suzanne M.
PY - 2019
Y1 - 2019
N2 - Recently, human ILCs that express CD117 and CD127 but lack CRTH2 and NKp44 have been shown to contain precursors of ILC1, ILC2, and ILC3. However, these ILCs have not been extensively characterized. We performed an unbiased hierarchical stochastic neighbor embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCs, which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, and the third expressed KLRG1, but not NKp46 or CD56. Analysis of their cytokine production profiles and transcriptome revealed that NKp46+ ILCs predominantly develop into ILC3s; some of them can differentiate into ILC1/NK-like cells, but they are unable to develop into ILC2s. In contrast, KLRG1+ ILCs predominantly differentiate into ILC2s. Single-cell cultures demonstrate that KLRG1+ ILCs can also differentiate into other ILC subsets depending on the signals they receive. Epigenetic profiling of KLRG1+ ILCs is consistent with the broad differentiation potential of these cells.
AB - Recently, human ILCs that express CD117 and CD127 but lack CRTH2 and NKp44 have been shown to contain precursors of ILC1, ILC2, and ILC3. However, these ILCs have not been extensively characterized. We performed an unbiased hierarchical stochastic neighbor embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCs, which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, and the third expressed KLRG1, but not NKp46 or CD56. Analysis of their cytokine production profiles and transcriptome revealed that NKp46+ ILCs predominantly develop into ILC3s; some of them can differentiate into ILC1/NK-like cells, but they are unable to develop into ILC2s. In contrast, KLRG1+ ILCs predominantly differentiate into ILC2s. Single-cell cultures demonstrate that KLRG1+ ILCs can also differentiate into other ILC subsets depending on the signals they receive. Epigenetic profiling of KLRG1+ ILCs is consistent with the broad differentiation potential of these cells.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071066921&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31201208
U2 - https://doi.org/10.1084/jem.20190490
DO - https://doi.org/10.1084/jem.20190490
M3 - Article
C2 - 31201208
SN - 0022-1007
VL - 216
SP - 1762
EP - 1776
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -