TY - JOUR
T1 - c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies
AU - Bernink, Jochem H.
AU - Ohne, Yoichiro
AU - Teunissen, Marcel B. M.
AU - Wang, Jingya
AU - Wu, Jincheng
AU - Krabbendam, Lisette
AU - Guntermann, Christine
AU - Volckmann, Richard
AU - Koster, Jan
AU - van Tol, Sophie
AU - Ramirez, Ivan
AU - Shrestha, Yashaswi
AU - de Rie, Menno A.
AU - Spits, Hergen
AU - Romero Ros, Xavier
AU - Humbles, Alison A.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - Cells, Cultured
KW - Humans
KW - Interleukin-17/immunology
KW - Interleukin-1beta/immunology
KW - Interleukin-23 Subunit p19/immunology
KW - Interleukin-4/immunology
KW - Lymphocytes/cytology
KW - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
KW - Proto-Oncogene Proteins c-kit/metabolism
KW - Psoriasis/immunology
KW - Receptors, CCR10/metabolism
KW - Skin/immunology
KW - Transforming Growth Factor beta/metabolism
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068549033&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31263279
UR - http://www.scopus.com/inward/record.url?scp=85068549033&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41590-019-0423-0
DO - https://doi.org/10.1038/s41590-019-0423-0
M3 - Article
C2 - 31263279
VL - 20
SP - 992
EP - 1003
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 8
ER -