Editors' ChoiceImmunology

More blurred lines with innate lymphoid cells

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Science Translational Medicine  24 Jul 2019:
Vol. 11, Issue 502, eaay3577
DOI: 10.1126/scitranslmed.aay3577


Group 2 innate lymphoid cells might form a pool of innate cells with capabilities beyond fighting parasites and mediating allergic diseases.

Innate lymphoid cells (ILCs) are a group of immune cells that develop from a common lymphoid progenitor, but they do not express an antigen specific receptor, a hallmark of adaptive immune cells. ILCs can be grouped according to their transcription factor and cytokine expression patterns. Group 2 ILCs (ILC2s) share some abilities of T helper 2 cells and are typically associated with allergic responses and antiparasite immunity. It has been known that ILCs can transdifferentiate from one subset into another, namely ILC2 into ILC1, but implications for human disease are only insufficiently understood. In this study, Bernink et al. describe an ILC2 subpopulation that can convert into interleukin-17 (IL-17)–producing ILC3-like cells. When looking for IL-17–producing ILCs isolated from the dermis of human skin upon stimulation with Candida albicans, they surprisingly found IL-17 to be predominantly produced in activated ILC2s. They further showed that ILC2s from peripheral adult blood and from neonatal cord blood, all had the ability to produce IL-17, including a subset with high levels of the skin-homing receptor CCR10. Importantly, this conversion was dependent on key inflammatory cytokines, such as IL-1β and IL-23.

Given this plasticity, the authors suggest that ILC2s are a substantial source of IL-17 in certain pathophysiological conditions. They found some evidence that the transition of ILC2 toward ILC3 might also occur in psoriasis, a prototypical IL-17–mediated disease. As ILC2s can also transdifferentiate into ILC1s, this remarkable plastic nature of ILC2 sheds a new light on this cell type as an important player in a potentially diverse range of immune responses. It will be interesting to understand the relative role of ILC subtype plasticity in specific diseases in more detail, but ILC2s, previously associated only with fighting parasites and mediating allergic diseases, might have a much broader role than originally assumed.

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