c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies

Jochem H. Bernink, Yoichiro Ohne, Marcel B. M. Teunissen, Jingya Wang, Jincheng Wu, Lisette Krabbendam, Christine Guntermann, Richard Volckmann, Jan Koster, Sophie van Tol, Ivan Ramirez, Yashaswi Shrestha, Menno A. de Rie, Hergen Spits, Xavier Romero Ros, Alison A. Humbles

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44− ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORγt, enabling the conversion into IL-17-producing cells in response to IL-1β and IL-23. We also report a role for transforming growth factor-β in promoting the conversion of c-Kit− ILC2s into RORγt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORγt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORγt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.
Original languageEnglish
Pages (from-to)992-1003
JournalNature Immunology
Volume20
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019
Externally publishedYes

Cite this

Bernink, J. H., Ohne, Y., Teunissen, M. B. M., Wang, J., Wu, J., Krabbendam, L., Guntermann, C., Volckmann, R., Koster, J., van Tol, S., Ramirez, I., Shrestha, Y., de Rie, M. A., Spits, H., Romero Ros, X., & Humbles, A. A. (2019). c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies. Nature Immunology, 20(8), 992-1003. https://doi.org/10.1038/s41590-019-0423-0