TY - JOUR
T1 - Identification of human cytotoxic ILC3s
AU - Krabbendam, Lisette
AU - Heesters, Balthasar A.
AU - Kradolfer, Chantal M. A.
AU - Spits, Hergen
AU - Bernink, Jochem H.
N1 - Funding Information: We thank B. Hooibrink, T.M.M. van Capel and K.I.M Brandwijk for help with flow cytometry. We thank Onze Lieve Vrouw Gasthuis, Amsterdam, the Netherlands for providing tonsils. This work is supported by the European Research Council (Advanced grant 341038 to H. Spits). B.A. Heesters is supported by a Veni fellowship (91618032) of the NWO (Netherlands Organization for Sciences). J.H. Bernink is supported by a ZonMw Veni fellowship (09.150.161.810.107) and a Dutch Lung Fund grant 4.2.18.237JO. Publisher Copyright: © 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
PY - 2021/4
Y1 - 2021/4
N2 - Human ILCs are classically categorized into five subsets; cytotoxic CD127−CD94+ NK cells and non-cytotoxic CD127+CD94−, ILC1s, ILC2s, ILC3s, and LTi cells. Here, we identify a previously unrecognized subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs resemble conventional ILC3s in terms of phenotype, transcriptome, and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs toward mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R1 expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
AB - Human ILCs are classically categorized into five subsets; cytotoxic CD127−CD94+ NK cells and non-cytotoxic CD127+CD94−, ILC1s, ILC2s, ILC3s, and LTi cells. Here, we identify a previously unrecognized subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs resemble conventional ILC3s in terms of phenotype, transcriptome, and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs toward mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R1 expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
KW - IL-12
KW - IL-15
KW - NK cells
KW - innate lymphoid cells
KW - tonsil
UR - http://www.scopus.com/inward/record.url?scp=85099741248&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.202048696
DO - https://doi.org/10.1002/eji.202048696
M3 - Article
C2 - 33300130
SN - 0014-2980
VL - 51
SP - 811
EP - 823
JO - European journal of immunology
JF - European journal of immunology
IS - 4
ER -