Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway
Abstract
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3). Despite recent advances, the cellular heterogeneity, developmental trajectory and signalling dependence of ILC progenitors are not fully understood. Here, using single-cell RNA-sequencing (scRNA-seq) of mouse bone marrow progenitors, we reveal ILC precursor subsets, delineate distinct ILC development stages and pathways, and report that high expression of programmed death 1 (PD-1 hi ) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1 hi IL-25R hi as an early checkpoint in ILC2 development, which was abolished by deficiency in the zinc-finger protein Bcl11b but restored by IL-25R overexpression. Similar to T lymphocytes, PD-1 was upregulated on activated ILCs. Administration of a PD-1 antibody depleted PD-1 hi ILCs and reduced cytokine levels in an influenza infection model in mice, and blocked papain-induced acute lung inflammat…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
scRNA-seq has been widely used to reveal the characteristics of immunity in different fields.
“It is notable that scRNA-seq has been widely used to reveal the characteristics of immunity in different fields. 6-10”
From Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis. (2020) · cites this paper as [10]
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
(2008) · Journal of Machine Learning Research · Cited by 33,051 · see citing works
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137 · see citing works
Innate lymphoid cells — a proposal for uniform nomenclature
Spits, H., Artis, D., Colonna, M., Diefenbach, A., Disanto, J. D., Eberl, G., Koyasu, S., Locksley, R., McKenzie, A., Mebius, R., et al. (2013) · Nature reviews. Immunology · doi:10.1038/nri3365 · Cited by 2,380 · see citing works
Self-citationImmune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345 · see citing works
The biology of innate lymphoid cells
Artis, D., & Spits, H. (2015) · Nature · doi:10.1038/nature14189 · Cited by 1,624 · see citing works
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes
Agata, Y., Kawasaki, A., Nishimura, H., Ishida, Y., Tsubat, T., Yagita, H., & Honjo, T. (1996) · International Immunology · doi:10.1093/intimm/8.5.765 · Cited by 1,589 · see citing works
Klose, C. S. N., Flach, M., Möhle, L., Rogell, L., Hoyler, T., Ebert, K., Fabiunke, C., Pfeifer, D., Sexl, V., Fonseca‐Pereira, D., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.030 · Cited by 1,081 · see citing works
Accounting for technical noise in single-cell RNA-seq experiments
Brennecke, P., Anders, S., Kim, J. K., Kołodziejczyk, A. A., Zhang, X., Proserpio, V., Baying, B., Benes, V., Teichmann, S. A., Marioni, J. C., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2645 · Cited by 979 · see citing works
Self-citationInnate lymphoid cells: A new paradigm in immunology
Eberl, G., Colonna, M., Di Santo, J. P., & McKenzie, A. N. J. (2015) · Science · doi:10.1126/science.aaa6566 · Cited by 878 · see citing works
Self-citationThe Transcription Factor GATA-3 Controls Cell Fate and Maintenance of Type 2 Innate Lymphoid Cells
Hoyler, T., Klose, C. S. N., Souabni, A., Turqueti‐Neves, A., Pfeifer, D., Rawlins, E. L., Voehringer, D., Busslinger, M., & Diefenbach, A. (2012) · Immunity · doi:10.1016/j.immuni.2012.06.020 · Cited by 855 · see citing works
Halim, T. Y. F., Krauss, R., Sun, A. C., & Takei, F. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.020 · Cited by 805 · see citing works
Huang, Y., Guo, L., Qiu, J., Chen, X., Hu‐Li, J., Siebenlist, U. K., Williamson, P. R., Urban, J. F., & Paul, W. E. (2014) · Nature Immunology · doi:10.1038/ni.3078 · Cited by 648 · see citing works
Self-citationRobinette, M. L., Fuchs, A. G., Cortez, V. S., Lee, J. S., Wang, Y., Durum, S. K., Gilfillan, S., & Colonna, M. (2015) · Nature Immunology · doi:10.1038/ni.3094 · Cited by 644 · see citing works
A committed hemopoietic precursor to innate lymphoid cells
Constantinides, M. G., McDonald, B. D., Verhoef, P., & Bendelac, A. (2014) · Nature · doi:10.1038/nature13047 · Cited by 503 · see citing works
Barlow, J. L., Bellosi, A., Hardman, C. S., Drynan, L. F., Wong, S. H., Cruickshank, J., & McKenzie, A. N. J. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.09.041 · Cited by 474 · see citing works
Self-citationA critical role for TCF-1 in T-lineage specification and differentiation
Weber, B., Chi, A. W. S., Chavez, A., Yashiro–Ohtani, Y., Yang, Q., Shestova, O. E., & Bhandoola, A. (2011) · Nature · doi:10.1038/nature10279 · Cited by 420 · see citing works
Yagi, R., Zhong, C., Northrup, D. L., Yu, F., Bouladoux, N. J., Spencer, S. P., Hu, G., Barron, L., Sharma, S., Nakayama, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.012 · Cited by 380 · see citing works
Transcriptional regulation of innate lymphoid cell fate
Serafini, N., Vosshenrich, C. A. J., & Santo, J. P. D. (2015) · Nature reviews. Immunology · doi:10.1038/nri3855 · Cited by 292 · see citing works
TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow
Yang, Q., Li, F., Harly, C., Xing, S., Ye, L., Xia, X., Wang, H., Wang, X., Yu, S., Zhou, X., et al. (2015) · Nature Immunology · doi:10.1038/ni.3248 · Cited by 292 · see citing works
Nfil3 is required for the development of all innate lymphoid cell subsets
Seillet, C., Rankin, L. C., Groom, J. R., Mielke, L. A., Tellier, J., Chopin, M., Huntington, N. D., Belz, G. T., & Carotta, S. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20140145 · Cited by 252 · see citing works
Self-citationYu, X., Wang, Y., Deng, M., Li, Y., Ruhn, K. A., Zhang, C. C., & Hooper, L. V. (2014) · eLife · doi:10.7554/elife.04406 · Cited by 244 · see citing works
Bcl11a is essential for lymphoid development and negatively regulates p53
Yu, Y., Wang, J., Khaled, W. T., Burke, S., Li, P., Chen, X., Yang, W., Jenkins, N. A., Copeland, N. G., Zhang, S., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20121846 · Cited by 223 · see citing works
Self-citationGata3 drives development of RORγt+ group 3 innate lymphoid cells
Serafini, N., Wolterink, R. G. J. K., Satoh‐Takayama, N., Xu, W., Vosshenrich, C. A. J., Hendriks, R. W., & Santo, J. P. D. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131038 · Cited by 203 · see citing works
Seehus, C. R., Aliahmad, P., de la Torre, B., Iliev, I. D., Spurka, L., Funari, V. A., & Kaye, J. G. (2015) · Nature Immunology · doi:10.1038/ni.3168 · Cited by 192 · see citing works
NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors
Xu, W., Domingues, R. G., Fonseca‐Pereira, D., Ferreira, M. M., Ribeiro, H., Lopez‐Lastra, S., Motomura, Y., Moreira-Santos, L., Bihl, F., Braud, V. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.057 · Cited by 184 · see citing works
Bcl11b is essential for group 2 innate lymphoid cell development
Walker, J. A., Oliphant, C. J., Englezakis, A., Yu, Y., Clare, S., Rodewald, H.-R., Belz, G. T., Liu, P., Fallon, P. G., & McKenzie, A. N. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20142224 · Cited by 166 · see citing works
Self-citationYu, Y., Wang, C., Clare, S., Wang, J., Lee, S.-C., Brandt, C., Burke, S., Lu, L., He, D., Jenkins, N. A., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20142318 · Cited by 163 · see citing works
Self-citationIshizuka, I. E., Chea, S., Gudjonson, H., Constantinides, M. G., Dinner, A. R., Bendelac, A. S., & Golub, R. (2016) · Nature Immunology · doi:10.1038/ni.3344 · Cited by 161 · see citing works
Jackson, J. T., Hu, Y., Liu, R., Masson, F., D’Amico, A., Carotta, S., Xin, A., Camilleri, M., Mount, A. M., Kallies, A., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.163 · Cited by 142 · see citing works
Self-citationMcConnell, M. J., Chevallier, N., Berkofsky‐Fessler, W., Giltnane, J. M., Malani, R. B., Staudt, L. M., & Licht, J. D. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9375-9388.2003 · Cited by 120 · see citing works
The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2
Zook, E. C., Ramirez, K., Guo, X., van der Voort, G., Sigvardsson, M., Svensson, E. C., Fu, Y., & Kee, B. L. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20150851 · Cited by 90 · see citing works
Kasagi, S., Kawano, S., Okazaki, T., Honjo, T., Morinobu, A., Hatachi, S., Shimatani, K., Tanaka, Y., Minato, N., & Kumagai, S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901652 · Cited by 87 · see citing works
Chea, S., Schmutz, S., Berthault, C., Perchet, T., Petit, M., Burlen‐Defranoux, O., Goldrath, A. W., Rodewald, H.-R., Cumano, A., & Golub, R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.015 · Cited by 84 · see citing works
Papain-induced asthma—physiological and immunological features
Novey, H. S., Marchioli, L. E., Sokol, W. N., & Wells, I. D. (1979) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(79)90198-2 · Cited by 78 · see citing works
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The diverse functions of the PD1 inhibitory pathway
Sharpe, A. H., & Pauken, K. E. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.108 · Cited by 1,980 · see citing works
Single-cell transcriptomics to explore the immune system in health and disease
Stubbington, M. J. T., Rozenblatt–Rosen, O., Regev, A., & Teichmann, S. A. (2017) · Science · doi:10.1126/science.aan6828 · Cited by 560 · see citing works
Self-citationS1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense
Huang, Y., Mao, K., Chen, X., Sun, M., Kawabe, T., Li, W., Usher, N. T., Zhu, J., Urban, J. F., Paul, W. E., et al. (2018) · Science · doi:10.1126/science.aam5809 · Cited by 551 · see citing works
Self-citationPatsoukis, N., Wang, Q., Strauss, L., & Boussiotis, V. A. (2020) · Science Advances · doi:10.1126/sciadv.abd2712 · Cited by 539 · see citing works
Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity
Colonna, M. (2018) · Immunity · doi:10.1016/j.immuni.2018.05.013 · Cited by 397 · see citing works
The Diverse Function of PD-1/PD-L Pathway Beyond Cancer
Qin, W., Hu, L.-P., Zhang, X., Jiang, S., Li, J., Zhang, Z., & Wang, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02298 · Cited by 371 · see citing works
ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity
Moral, J. A., Leung, J., Rojas, L. A., Ruan, J. J., Zhao, J. N., Sethna, Z. M., Ramnarain, A., Gasmi, B., Gururajan, M., Redmond, D., et al. (2020) · Nature · doi:10.1038/s41586-020-2015-4 · Cited by 343 · see citing works
Crosstalk Between Gut Microbiota and Innate Immunity and Its Implication in Autoimmune Diseases
Jiao, Y., Wu, L., Huntington, N. D., & Zhang, X. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00282 · Cited by 321 · see citing works
Functional interactions between innate lymphoid cells and adaptive immunity
Sonnenberg, G. F., & Hepworth, M. R. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0194-8 · Cited by 271 · see citing works
Revolutionizing immunology with single-cell RNA sequencing
Chen, H., Ye, F., & Guo, G. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0214-4 · Cited by 237 · see citing works
Skin-resident innate lymphoid cells converge on a pathogenic effector state
Bielecki, P., Riesenfeld, S. J., Hütter, J.-C., Triglia, E. T., Kowalczyk, M. S., Ricardo-González, R. R., Lian, M., Vesely, M. C. A., Kroehling, L., Xu, H. Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03188-w · Cited by 218 · see citing works
Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis.
Hua, X., Hu, G., Hu, Q., Chang, Y., Hu, Y., Gao, L., Chen, X., Yang, P.-C., Zhang, Y., Li, M., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.043545 · Cited by 201 · see citing works
Self-citationPD-1 regulates KLRG1+ group 2 innate lymphoid cells
Taylor, S. R., Huang, Y., Mallett, G., Stathopoulou, C., Felizardo, T. C., Sun, M., Martin, E. L., Zhu, N., Woodward, E. L., Elias, M. S., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161653 · Cited by 203 · see citing works
Functional and phenotypic heterogeneity of group 3 innate lymphoid cells
Melo-González, F., & Hepworth, M. R. (2016) · Immunology · doi:10.1111/imm.12697 · Cited by 199 · see citing works
Emerging concepts in PD-1 checkpoint biology
Pauken, K. E., Torchia, J. A., Chaudhri, A., Sharpe, A. H., & Freeman, G. J. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101480 · Cited by 196 · see citing works
Innate lymphoid cells control signaling circuits to regulate tissue-specific immunity
Klose, C. S. N., & Artis, D. (2020) · Cell Research · doi:10.1038/s41422-020-0323-8 · Cited by 195 · see citing works
Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses
Gurram, R. K., & Zhu, J. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0210-8 · Cited by 187 · see citing works
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma
Jacquelot, N., Seillet, C., Wang, M., Pizzolla, A., Liao, Y., Hediyeh-zadeh, S., Grisaru‐Tal, S., Louis, C., Huang, Q., Schreuder, J., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00943-z · Cited by 183 · see citing works
Self-citationInnate Lymphoid Cell Development: A T Cell Perspective
Cherrier, D. E., Serafini, N., & Di Santo, J. P. (2018) · Immunity · doi:10.1016/j.immuni.2018.05.010 · Cited by 181 · see citing works
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity
Yudanin, N. A., Schmitz, F., Flamar, A.-L., Thome, J. J. C., Wojno, E. D. T., Moeller, J. B., Schirmer, M., Latorre, I. J., Xavier, R. J., Färber, D. L., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.012 · Cited by 178 · see citing works
PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity
Helou, D. G., Shafiei-Jahani, P., Lo, R., Howard, E. D., Hurrell, B. P., Galle-Treger, L., Painter, J. D., Lewis, G. M., Soroosh, P., Sharpe, A. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17813-1 · Cited by 180 · see citing works
Fang, D., & Zhu, J. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170494 · Cited by 175 · see citing works
Quatrini, L., Mariotti, F. R., Munari, E., Tumino, N., Vacca, P., & Moretta, L. (2020) · Cancers · doi:10.3390/cancers12113285 · Cited by 162 · see citing works
An Id2RFP-Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials
Xu, W., Cherrier, D. E., Chea, S., Vosshenrich, C. A. J., Serafini, N., Petit, M., Liu, P., Golub, R., & Santo, J. P. D. (2019) · Immunity · doi:10.1016/j.immuni.2019.02.022 · Cited by 157 · see citing works
Self-citationMinimal PD-1 expression in mouse and human NK cells under diverse conditions
Judge, S. J., Dunai, C., Aguilar, E. G., Vick, S. C., Sturgill, I. R., Khuat, L. T., Stoffel, K. M., Dyke, J. V., Longo, D. L., Darrow, M. A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133353 · Cited by 142 · see citing works
The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage
Harly, C., Kenney, D., Ren, G., Lai, B., Raabe, T. D., Yang, Q., Cam, M. C., Xue, H., Zhao, K., & Bhandoola, A. (2019) · Nature Immunology · doi:10.1038/s41590-019-0445-7 · Cited by 124 · see citing works
Walker, J. A., Clark, P. A., Crisp, A., Barlow, J. L., Szeto, A. C. H., Ferreira, A. C. F., Rana, B. M. J., Jolin, H. E., Rodríguez‐Rodríguez, N., Sivasubramaniam, M., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.05.002 · Cited by 130 · see citing works
Self-citationILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
Schwartz, C., Khan, A. R., Floudas, A., Saunders, S. P., Hams, E., Rodewald, H.-R., McKenzie, A. N. J., & Fallon, P. G. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170051 · Cited by 128 · see citing works
Self-citationDevelopment and differentiation of early innate lymphoid progenitors
Harly, C., Cam, M., Kaye, J., & Bhandoola, A. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20170832 · Cited by 125 · see citing works
Lessel, D., Gehbauer, C., Bramswig, N. C., Schluth‐Bolard, C., Venkataramanappa, S., van Gassen, K. L. I., Hempel, M., Haack, T. B., Barešić, A., Genetti, C. A., et al. (2018) · Brain · doi:10.1093/brain/awy173 · Cited by 121 · see citing works
Self-citationUsing omics approaches to understand pulmonary diseases
Kan, M., Shumyatcher, M., & Himes, B. E. (2017) · Respiratory Research · doi:10.1186/s12931-017-0631-9 · Cited by 124 · see citing works
Understanding development and stem cells using single cell-based analyses of gene expression
Kumar, P., Tan, Y., & Cahan, P. (2017) · Development · doi:10.1242/dev.133058 · Cited by 117 · see citing works
Rethinking immune checkpoint blockade: ‘Beyond the T cell’
Liu, X., Hogg, G. D., & DeNardo, D. G. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001460 · Cited by 120 · see citing works
Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets
Ghaedi, M., Shen, S., Orangi, M., Martínez-González, I., Wei, L. L., Lu, X., Das, A., Heravi‐Moussavi, A., Marra, M. A., Bhandoola, A., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182293 · Cited by 110 · see citing works
Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16
Hosokawa, H., Romero-Wolf, M., Yui, M. A., Ungerbäck, J., Quiloan, M. L. G., Matsumoto, M., Nakayama, K. I., Tanaka, T., & Rothenberg, E. V. (2018) · Nature Immunology · doi:10.1038/s41590-018-0238-4 · Cited by 108 · see citing works
Li, Q., Li, D., Zhang, X., Wan, Q., Zhang, W., Zheng, M., Zou, L., Elly, C., Lee, J. H., & Liu, Y. (2018) · Immunity · doi:10.1016/j.immuni.2017.12.013 · Cited by 106 · see citing works
scRNASeqDB: A Database for RNA-Seq Based Gene Expression Profiles in Human Single Cells
Cao, Y., Zhu, J., Han, G., Jia, P., & Zhao, Z. (2017) · Genes · doi:10.3390/genes8120368 · Cited by 104 · see citing works
Gastrointestinal toxicity of immune checkpoint inhibitors: From mechanisms to management
Samaan, M. A., Pavlidis, P., Papa, S., Powell, N., & Irving, P. M. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2018.14 · Cited by 100 · see citing works
Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
Rothenberg, E. V., Hosokawa, H., & Ungerbäck, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00228 · Cited by 99 · see citing works
Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule
Ben Nasr, M., Usuelli, V., Dellepiane, S., Seelam, A. J., Fiorentino, T. V., D’Addio, F., Fiorina, E., Xu, C., Xie, Y., Balasubramanian, H. B., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.05.001 · Cited by 102 · see citing works
Regulatory T cells and type 2 innate lymphoid cell‐dependent asthma
Aron, J., & Akbari, O. (2017) · Allergy · doi:10.1111/all.13139 · Cited by 96 · see citing works
The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation
Holmes, T. D., Pandey, R. V., Helm, E. Y., Schlums, H., Han, H., Campbell, T. M., Drashansky, T. T., Chiang, S. C. C., Wu, C.-Y., Tao, C., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abc9801 · Cited by 94 · see citing works
Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System
Withers, D. R., & Hepworth, M. R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01298 · Cited by 96 · see citing works
Cytotoxic granzyme C–expressing ILC1s contribute to antitumor immunity and neonatal autoimmunity
Nixon, B. G., Chou, C., Krishna, C., Dadi, S., Michel, A. O., Cornish, A. E., Kansler, E. R., Do, M. H., Wang, X., Capistrano, K. J., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abi8642 · Cited by 95 · see citing works
Zhong, C., Zheng, M., Cui, K., Martins, A. J., Hu, G., Li, D., Tessarollo, L., Kozlov, S. V., Keller, J. R., Tsang, J. S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.12.001 · Cited by 94 · see citing works
Self-citationGroup 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis
Mindt, B. C., Fritz, J. H., & Duerr, C. U. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00840 · Cited by 93 · see citing works
Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer
Chen, Y.-Y., & Tian, Z. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00561-z · Cited by 83 · see citing works
Systems Immunology: Learning the Rules of the Immune System
Villani, A., Sarkizova, S., & Hacohen, N. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053035 · Cited by 84 · see citing works
Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells
Mortha, A., & Burrows, K. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00191 · Cited by 84 · see citing works
Kadel, S., Ainsua‐Enrich, E., HATİPOGLU, I. H., Turner, S., Singh, S. P., Khan, S., & Kovats, S. (2018) · ImmunoHorizons · doi:10.4049/immunohorizons.1800008 · Cited by 83 · see citing works
Immunology in the Era of Single-Cell Technologies
Efremova, M., Vento‐Tormo, R., Park, J.-E., Teichmann, S. A., & James, K. R. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090419-020340 · Cited by 77 · see citing works
Self-citationGATA3 Regulates the Development and Functions of Innate Lymphoid Cell Subsets at Multiple Stages
Zhu, J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01571 · Cited by 79 · see citing works
Visualization of Single Cell RNA-Seq Data Using t-SNE in R
Zhou, B., & Jin, W. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0301-7_8 · Cited by 78 · see citing works
Tracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration
Yang, Y., Chu, C., Liu, L., Wang, C., Hu, C., Rung, S., Man, Y., & Qu, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-41608-9 · Cited by 80 · see citing works
Self-citationMariotti, F. R., Quatrini, L., Munari, E., Vacca, P., & Moretta, L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00910 · Cited by 75 · see citing works
Cellular pathways in the development of human and murine innate lymphoid cells
Scoville, S. D., Freud, A. G., & Caligiuri, M. A. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.11.003 · Cited by 76 · see citing works
Pulmonary group 2 innate lymphoid cells: surprises and challenges
Starkey, M. R., McKenzie, A. N. J., Belz, G. T., & Hansbro, P. M. (2019) · Mucosal Immunology · doi:10.1038/s41385-018-0130-4 · Cited by 77 · see citing works
Self-citationOherle, K., Acker, E., Bonfield, M., Wang, T., Gray, J. K., Lang, I., Bridges, J. P., Lewkowich, I. P., Xu, Y. J., Ahlfeld, S. K., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.01.005 · Cited by 74 · see citing works
The Whole Body as the System in Systems Immunology
Poon, M. M. L., & Färber, D. L. (2020) · iScience · doi:10.1016/j.isci.2020.101509 · Cited by 74 · see citing works
Helper-like Innate Lymphoid Cells in Humans and Mice
Guia, S., & Narni-Mancinelli, É. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.03.002 · Cited by 70 · see citing works
Pulanco, M. C., Madsen, A. T., Tanwar, A., Corrigan, D. T., & Zang, X. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01019-8 · Cited by 68 · see citing works
Developmental options and functional plasticity of innate lymphoid cells
Lim, A. I., Verrier, T., Vosshenrich, C. A. J., & Santo, J. P. D. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.03.010 · Cited by 69 · see citing works
Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells
Hosokawa, H., Romero-Wolf, M., Yang, Q., Motomura, Y., Levanon, D., Groner, Y., Moro, K., Tanaka, T., & Rothenberg, E. V. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190972 · Cited by 67 · see citing works
On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19
Gambichler, T., Reuther, J., Scheel, C., & Becker, J. C. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001145 · Cited by 67 · see citing works
Wang, X., Shen, X., Chen, S., Liu, H., Hong, N., Zhong, H., Chen, X. X., & Jin, W. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100581 · Cited by 67 · see citing works
Self-citationNatural killers or ILC1s? That is the question
Seillet, C., Brossay, L., & Vivier, É. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.08.009 · Cited by 66 · see citing works
JAK / STAT signaling in regulation of innate lymphoid cells: The gods before the guardians
Stabile, H., Scarno, G., Fionda, C., Gismondi, A., Santoni, A., Gadina, M., & Sciumè, G. (2018) · Immunological Reviews · doi:10.1111/imr.12705 · Cited by 66 · see citing works
Sachamitr, P., Leishman, A. J., Davies, T. J., & Fairchild, P. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01935 · Cited by 64 · see citing works
Notch signaling at the crossroads of innate and adaptive immunity
Vanderbeck, A., & Maillard, I. P. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ri0520-138r · Cited by 61 · see citing works
Wang, X., Peng, H. C., & Tian, Z. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0212-6 · Cited by 62 · see citing works
Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions
Sudo, T., Motomura, Y., Okuzaki, D., Hasegawa, T., Yokota, T., Kikuta, J., Ao, T., Mizuno, H., Matsui, T., Motooka, D., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20200817 · Cited by 61 · see citing works
NK Cell Development in Times of Innate Lymphoid Cell Diversity
Stokic-Trtica, V., Diefenbach, A., & Klose, C. S. N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00813 · Cited by 61 · see citing works
Fei, Q., Pan, Y., Lin, W., Zhou, Y., Yu, X., Hou, Z., Yu, X., Lin, X., Lin, R., Lu, F., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02787-1 · Cited by 60 · see citing works
Macrophage heterogeneity and energy metabolism
Verdeguer, F., & Aouadi, M. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.03.043 · Cited by 59 · see citing works
The Innate Immune Response in Myocardial Infarction, Repair, and Regeneration
Gentek, R., & Hoeffel, G. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-57613-8_12 · Cited by 56 · see citing works
Innate Lymphoid Cells of the Lung
Barlow, J. L., & McKenzie, A. N. J. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114630 · Cited by 58 · see citing works
Self-citationType 2 innate lymphoid cells in the induction and resolution of tissue inflammation
Wallrapp, A., Riesenfeld, S. J., Burkett, P. R., & Kuchroo, V. K. (2018) · Immunological Reviews · doi:10.1111/imr.12702 · Cited by 57 · see citing works
Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection
Sharif‐Askari, N. S., Sharif‐Askari, F. S., Mdkhana, B., Heialy, S. A., AlSafar, H. S., Hamoudi, R., Hamid, Q. A., & Halwani, R. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.11.002 · Cited by 54 · see citing works
Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes
Pesce, S., Trabanelli, S., Vito, C. D., Greppi, M., Obino, V., Guolo, F., Minetto, P., Bozzo, M., Calvi, M., Zaghi, E., et al. (2020) · Cancers · doi:10.3390/cancers12123504 · Cited by 53 · see citing works
Qian, L., Bajaña, S., Georgescu, C., Peng, V., Wang, H., Adrianto, I., Colonna, M., Alberola‐Ila, J., Wren, J. D., & Sun, X.-H. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182100 · Cited by 50 · see citing works
Liu, S., Sirohi, K., Verma, M., McKay, J. T., Michalec, L., Sripada, A., Danhorn, T., Rollins, D. R., Good, J. T., Gorska, M. M., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.01.038 · Cited by 52 · see citing works
The depths of PD-1 function within the tumor microenvironment beyond CD8+ T cells
Laba, S., Mallett, G., & Amarnath, S. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.022 · Cited by 51 · see citing works
Ryu, S., Lim, M., Kim, J., & Kim, H. Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01022-z · Cited by 51 · see citing works
Transcriptional regulators dictate innate lymphoid cell fates
Zhong, C., & Zhu, J. (2017) · Protein & Cell · doi:10.1007/s13238-017-0369-7 · Cited by 51 · see citing works
Jak3 deficiency blocks innate lymphoid cell development
Robinette, M. L., Cella, M., Telliez, J., Ulland, T. K., Barrow, A. D., Capuder, K., Gilfillan, S., Lin, L.-L., Notarangelo, L. D., & Colonna, M. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.38 · Cited by 51 · see citing works
Progress and applications of single-cell sequencing techniques
Yasen, A., Aini, A., Wang, H., Li, W., Zhang, C., Ran, B., Tuxun, T., Maimaitinijiati, Y., Shao, Y., Aji, T., et al. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104198 · Cited by 51 · see citing works
Wu, D., Hu, L., Han, M., Deng, Y., Zhang, Y., Ren, G., Zhao, X., Li, Z., Li, P., Zhang, Y., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00595-9 · Cited by 50 · see citing works
Tissue-Resident Lymphocytes Across Innate and Adaptive Lineages
Chou, C., & Li, M. O. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02104 · Cited by 50 · see citing works
Group 2 Innate Lymphoid Cells in Human Respiratory Disorders
van der Ploeg, E. K., Mascaro, A. C., Huylebroeck, D., Hendriks, R. W., & Stadhouders, R. (2019) · Journal of Innate Immunity · doi:10.1159/000496212 · Cited by 49 · see citing works
Natural killer cells and type 1 innate lymphoid cells in cancer
Lopes, N., Vivier, É., & Narni-Mancinelli, É. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2022.101709 · Cited by 48 · see citing works
Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus
Wang, H.-C., Qian, L., Zhao, Y. L., Mengarelli, J., Adrianto, I., Montgomery, C. G., Urban, J. F., Fung, K.-M. A., & Sun, X.-H. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1602009 · Cited by 48 · see citing works
Loyon, R., Jary, M., Salomé, B., Gomez‐Cadena, A., Galaine, J., Kroemer, M., Romero, P. J., Trabanelli, S., Adotévi, O., Borg, C., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02121 · Cited by 47 · see citing works
Innate lymphoid cell development
Ghaedi, M., & Takei, F. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.03.009 · Cited by 47 · see citing works
Innate lymphoid cells and cancer: Role in tumor progression and inhibition
Yuan, X., Rasul, F., Nashan, B., & Sun, C. (2021) · European Journal of Immunology · doi:10.1002/eji.202049033 · Cited by 46 · see citing works
Resisting Resistance to Immune Checkpoint Therapy: A Systematic Review
Haibe, Y., Husseini, Z. E., Sayed, R. E., & Shamseddine, A. I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176176 · Cited by 45 · see citing works
Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages
Kasal, D. N., & Bendelac, A. S. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200487 · Cited by 44 · see citing works
Stehle, C., Rückert, T., Fiancette, R., Gajdasik, D. W., Willis, C., Ulbricht, C., Durek, P., Mashreghi, M., Finke, D., Hauser, A. E., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-01029-6 · Cited by 44 · see citing works
Differential Modulation of Human Innate Lymphoid Cell (ILC) Subsets by IL-10 and TGF-β
Bonne-Année, S., Bush, M. C., & Nutman, T. B. (2019) · Scientific Reports · doi:10.1038/s41598-019-50308-8 · Cited by 43 · see citing works
Organoids capture tissue-specific innate lymphoid cell development in mice and humans
Jowett, G. M., Read, E., Roberts, L. B., Coman, D., González, M. V., Zabinski, T., Niazi, U. H. K., Reis, R. A. D., Trieu, T.-J., Danovi, D., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111281 · Cited by 42 · see citing works
Bone Marrow NK Cells: Origin, Distinctive Features, and Requirements for Tissue Localization
Bonanni, V., Sciumè, G., Santoni, A., & Bernardini, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01569 · Cited by 44 · see citing works
- Authors
- Yu, Y., Tsang, J. C. H., Wang, C., Clare, S., Wang, J., Chen, X., Brandt, C., Kane, L., Campos, L. S., Lu, L., Belz, G. T., McKenzie, A. N. J., Teichmann, S. A., Dougan, G., & Liu, P.
- Affiliations
- Wellcome Sanger Institute (GB)
- Chinese University of Hong Kong (HK)
- Shanghai Jiao Tong University (CN)
- The University of Melbourne (AU)
- MRC Laboratory of Molecular Biology (GB)
- European Bioinformatics Institute (GB)
- Corresponding author
- Liu, Pentao
- ORCID
- Venue
- Nature
- Published
- 2016-09-29
- Volume
- 539
- Issue
- 7627
- Pages
- 102-106
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2525469791
- Cited by
- 306
- References
- 41
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 23 · 2023: 27 · 2022: 35 · 2021: 36 · 2020: 46 · 2019: 39 · 2018: 32 · 2017: 31 · 2016: 1 · 2014: 1
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Wellcome Trust (100963/Z/13/Z, 098051)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- innate lymphoid cells, PD-1, BCL11B, IL-25 receptor, influenza, acute lung inflammation, bone marrow progenitor cells, cytokine production, tissue homeostasis
- MeSH terms
- Animals, Antibodies, Base Sequence, Cell Differentiation, Cell Separation, Disease Models, Animal, Humans, Immunity, Innate, Immunotherapy, Influenza, Human, Killer Cells, Natural, Lymphocyte Activation, Lymphocytes, Mice, Inbred C57BL, Pneumonia, Repressor Proteins, T-Lymphocytes, Cytokines, Receptors, Interleukin, Cell Lineage, Tumor Suppressor Proteins, Mice, Lymphoid Progenitor Cells, Single-Cell Analysis, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review