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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.

SUBMITTER: Krabbendam L

PROVIDER: S-EPMC8248192 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Identification of human cytotoxic ILC3s.

Krabbendam Lisette L Heesters Balthasar A BA Kradolfer Chantal M A CMA Spits Hergen H Bernink Jochem H JH

European journal of immunology 20210127 4

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 cytot ...[more]

PMID: 33300130

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Identification of human cytotoxic ILC3s

Project description: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 novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly 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 towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or 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.

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