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

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.

• Authors: 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
• Journal: Nature immunology (Nat Immunol) Vol. 20 Issue 8 Pg. 992-1003 (08 2019) ISSN: 1529-2916 [Electronic] United States
• PMID: 31263279 (Publication Type: Journal Article)

Chemical References

• CCR10 protein, human
• IL17A protein, human
• IL1B protein, human
• IL23A protein, human
• IL4 protein, human
• Interleukin-17
• Interleukin-1beta
• Interleukin-23 Subunit p19
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RORC protein, human
• Receptors, CCR10
• Transforming Growth Factor beta
• Interleukin-4
• KIT protein, human
• Proto-Oncogene Proteins c-kit

Topics

• Cells, Cultured
• Humans
• Interleukin-17 (immunology)
• Interleukin-1beta (immunology)
• Interleukin-23 Subunit p19 (immunology)
• Interleukin-4 (immunology)
• Lymphocytes (cytology, immunology)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• Proto-Oncogene Proteins c-kit (metabolism)
• Psoriasis (immunology, pathology)
• Receptors, CCR10 (metabolism)
• Skin (immunology, pathology)
• Transforming Growth Factor beta (metabolism)