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Identification of human cytotoxic ILC3s
Lisette Krabbendam1, Balthasar A Heesters1, Chantal M A Kradolfer1
1Amsterdam UMC, Department of Experimental Immunology, University of Amsterdam, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam, Amsterdam, The Netherlands.
European Journal of Immunology
|December 10, 2020
Summary
Scientists discovered a new human ILC subset that is cytotoxic yet retains helper ILC markers. These CD94+ ILCs produce IL-22 and can gain cytotoxicity without becoming NK cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human innate lymphoid cells (ILCs) are classified into five subsets, including cytotoxic NK cells and non-cytotoxic ILC1s, ILC2s, ILC3s, and LTi cells.
- Existing classifications distinguish between cytotoxic NK cells and non-cytotoxic helper ILCs.
Purpose of the Study:
- To identify and characterize a novel subset of ILCs within the CD127+ population.
- To investigate the cytotoxic potential and differentiation capacity of this newly identified ILC subset.
Main Methods:
- Phenotypic analysis using flow cytometry, focusing on CD127 and CD94 expression.
- Transcriptomic profiling to compare the novel subset with conventional ILCs.
- Cytokine production assays in response to IL-15 and IL-12 stimulation.
Main Results:
- A previously unrecognized CD94+ ILC subset was identified within the CD127+ ILC population.
- These CD94+ ILCs exhibited a phenotype, transcriptome, and cytokine profile similar to ILC3s but possessed high cytotoxicity.
- IL-15 did not induce NK cell differentiation; instead, these cells maintained RORγt, CD127, and CD200R1 expression, producing IL-22.
- IL-12 stimulation induced CD94 expression and cytotoxicity in non-cytotoxic ILC3s, an effect not seen with IL-15.
Conclusions:
- Human helper ILCs can acquire a cytotoxic program without undergoing terminal differentiation into NK cells.
- This finding expands the understanding of ILC plasticity and functional diversity in humans.
