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Comment on: Evidence of innate lymphoid cell redundancy in humans

Nature Immunology volume 19, pages 788–789 (2018)Cite this article

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To the Editor: A 2016 study by Vély et al. suggests that innate lymphocytes, including innate lymphoid cells (ILCs) and natural killer (NK) cells, are dispensable in the control of human disease, at least in the presence of functioning adaptive immunity and under modern living conditions1. Their conclusions are based on cohort studies of patients with severe combined immune deficiency (SCID) due to mutations in the gene encoding the tyrosine kinase JAK3 (JAK3) or the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ (IL2RG) who had an extremely low or undetectable number of ILCs and NK cells after non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT)1. These findings are important additions to the literature, and investigation of such rare patient populations with long-term follow-up (up to 39 years) is to be commended.

As noted in the accompanying News and Views by Weinkove et al., however, limitations of the study include the small sample size, the limited number of tissue samples with which to investigate resident ILCs, and the suggestion of infectious susceptibility with a lack of innate lymphocytes, with almost half of patients having infection with human papilloma virus (HPV)2. Despite this, we have become aware of an emerging viewpoint in the field that NK cells are not required for health in an otherwise immunocompetent patient, on the basis of the findings from this single study. Here, we respectfully offer additional evidence that human NK cells are an essential, non-redundant component of the human immune system.

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Authors and Affiliations

  1. Department of Pediatrics, Columbia University, New York, NY, USA

    Jordan S. Orange & Emily M. Mace

  2. Department of Pediatrics, Division of Rheumatology, Washington University, St. Louis, MO, USA

    Anthony R. French & Megan A. Cooper

  3. Department of Medicine, Division of Rheumatology, Washington University, St. Louis, MO, USA

    Wayne M. Yokoyama

  4. Department of Medicine, Division of Oncology, Washington University, St. Louis, MO, USA

    Todd A. Fehniger

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  1. Jordan S. Orange
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Correspondence to Megan A. Cooper.

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Competing interests

T.A.F. is a member of the scientific advisory board for Cyto-Sen Therapeutics and receives research funding from Celgene, Affimed and Altor BioScience.

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Orange, J.S., Mace, E.M., French, A.R. et al. Comment on: Evidence of innate lymphoid cell redundancy in humans. Nat Immunol 19, 788–789 (2018). https://doi.org/10.1038/s41590-018-0164-5

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