TY - JOUR
T1 - Tissue signals imprint ILC2 identity with anticipatory function
AU - Ricardo-Gonzalez, Roberto R.
AU - Van Dyken, Steven J.
AU - Schneider, Christoph
AU - Lee, Jinwoo
AU - Nussbaum, Jesse C.
AU - Liang, Hong Erh
AU - Vaka, Dedeepya
AU - Eckalbar, Walter L.
AU - Molofsky, Ari B.
AU - Erle, David J.
AU - Locksley, Richard M.
N1 - Funding Information:
We thank M. Consengco and M. Ji for technical expertise; Z. Wang for cell sorting; A. Barczak, R. Barbeau, and J. Pollack for assistance with RNA-seq; E. Wan for assistance with scRNA-seq; J. Turnbaugh (University of California San Francisco) for providing germ-free mice; and M. Ansel and A. Marson for comments on the manuscript. This work was supported by the National Institutes of Health (AI030663 and HL128903 to R.M.L., AI122702 to J.L., DK101604 to A.B.M., and AI113143 to J.C.N.), Dermatology Foundation (R.R.R.-G.), A.P. Giannini Foundation (R.R.R.-G.), Robert Wood Johnson Foundation (R.R.R.-G.), Swiss National Science Foundation (P2EZP3_162266 and P300PA_171591 to C.S.), Howard Hughes Medical Institute (R.M.L.), and the Sandler Asthma Basic Research Center at the University of California San Francisco (R.M.L).
Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life.
AB - Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life.
UR - http://www.scopus.com/inward/record.url?scp=85053319624&partnerID=8YFLogxK
U2 - 10.1038/s41590-018-0201-4
DO - 10.1038/s41590-018-0201-4
M3 - Article
C2 - 30201992
AN - SCOPUS:85053319624
VL - 19
SP - 1093
EP - 1099
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 10
ER -