Identification of human cytotoxic ILC3s

Lisette Krabbendam; Balthasar A Heesters; Chantal M A Kradolfer; Hergen Spits; Jochem H Bernink

doi:10.1002/eji.202048696

Identification of human cytotoxic ILC3s

Lisette Krabbendam
, Balthasar A Heesters
, Chantal M A Kradolfer
, Hergen Spits
, Jochem H Bernink

University of Amsterdam, VU University Amsterdam

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	811-823
Number of pages	13
Journal	European Journal of Immunology
Volume	51
Issue number	4
DOIs	https://doi.org/10.1002/eji.202048696
Publication status	Published - Apr 2021

Bibliographical note

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

Keywords

IL-12
IL-15
NK cells
innate lymphoid cells
tonsil

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title = "Identification of human cytotoxic ILC3s",

abstract = "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.",

keywords = "IL-12, IL-15, NK cells, innate lymphoid cells, tonsil",

author = "Lisette Krabbendam and Heesters, \{Balthasar A\} and Kradolfer, \{Chantal M A\} and Hergen Spits and Bernink, \{Jochem H\}",

note = "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: {\textcopyright} 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH",

year = "2021",

month = apr,

doi = "10.1002/eji.202048696",

language = "English",

volume = "51",

pages = "811--823",

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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 - https://www.scopus.com/pages/publications/85099741248

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DO - 10.1002/eji.202048696

M3 - Article

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SN - 0014-2980

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EP - 823

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 4

ER -

Identification of human cytotoxic ILC3s

Abstract

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Keywords

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