Identification of human cytotoxic ILC3s

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

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17 Citations (Scopus)


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 languageEnglish
Pages (from-to)811-823
Number of pages13
JournalEuropean journal of immunology
Issue number4
Early online date2020
Publication statusPublished - Apr 2021


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

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