The DOI matches its Crossref record; 119 of the 122 references it cites were found in a registry or an index.
The chromatin landscape of Th17 cells reveals mechanisms of diversification of regulatory and pro-inflammatory states
Open accessAbstract
Th17 cells are a heterogenous cell population consisting of non-pathogenic Th17 cells (npTh17) that contribute to tissue homeostasis and pathogenic Th17 cells (pTh17) that are potent mediators of tissue inflammation. To reveal regulatory mechanisms underlying Th17 heterogeneity, we performed combined ATAC-seq and RNA-seq and discovered substantial differences in the chromatin landscape of npTh17 and pTh17 cells both in vitro and in vivo . Compared to other CD4 + T cell subsets, npTh17 cells share accessible chromatin programs with T regs , and pTh17 cells have an intermediate profile spanning features of npTh17 cells and Th1 cells. Integrating single-cell ATAC-seq and single-cell RNA-seq, we inferred self-reinforcing and mutually exclusive regulatory networks controlling the different cell states and predicted transcription factors (TFs) shaping the chromatin landscape of Th17 cell pathogenicity. We validated one novel TF, BACH2, which promotes immunomodulatory npTh17 programs and restrains pro-inflammatory Th1-like programs in Th17 cells and showed genetic evidence for protective variants in the human BACH2 locus associated with multiple sclerosis. Our work uncovered mechanisms that regulate Th17 heterogeneity, revealed shared regulatory programs with other CD4 + T cell subsets, and identified novel drivers of Th17 pathogenicity as potential targets to mitigate autoimmunity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“analysis of Th17 cells in different tissue sites has revealed that Th17 cells may exhibit distinct transcriptional profiles associated with either homeostatic or pathogenic functions”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“we profiled Th17 cells from multiple tissues of naïve IL-17-fate reporter mice by single-cell RNA-seq”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“tissue Th17 cells were found to exhibit tissue-specific transcriptomic signatures”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Under inflammatory conditions, tissue Th17 cells have been reported to exhibit plastic changes in their effector programs.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Use of cell fate reporter mice showed that T cells that initially express IL-17 (ex-Th17 cells) can subsequently express proinflammatory cytokines, including IFNγ and GM-CSF [38, 76].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“We identified IL-23-signaling as a main driver of the conversion of homeostatic IL-17A/F+ SLAMF6+ cells to pathogenic IFNγ+ GM-CSF+ CXCR6+ cells in EAE [38].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Hence, we propose GM-CSF expression as part of a general pathogenic program together with other pro-inflammatory molecules such as BHLHE40, IFNγ, and CXCR6 that can be induced across multiple T helper cell subsets [33, 38, 177].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“A recent study from one of our laboratories, using fate reporter mice, provides strong in vivo support for the notion that homeostatic Th17 cells differentiate into inflammatory Th17 cells that mediate autoimmune disease.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Using single cell genomics, we identified a homeostatic IL-17A/F+ population, marked by SLAMF6, that gives rise to a pathogenic IFNγ+ GM-CSF+ population marked by CXCR6 during EAE [38], suggesting a direct in vivo relationship between these cells.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Self-citationMcCarthy, D. J., Chen, Y., & Smyth, G. K. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks042 · Cited by 5,195
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Self-citationGREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502 · cited 2×
“Peak annotation with target genes was performed using GREAT (version 4.0.4; http://great.stanford.edu/public/html/) with default parameters 74 .”
InfluentialWard’s Hierarchical Agglomerative Clustering Method: Which Algorithms Implement Ward’s Criterion?
Murtagh, F. D., & Legendre, P. (2014) · Journal of Classification · doi:10.1007/s00357-014-9161-z · Cited by 4,208
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
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717
Easy quantitative assessment of genome editing by sequence trace decomposition
Brinkman, E. K., Chen, T., Amendola, M., & van Steensel, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku936 · Cited by 2,390
Genetic and epigenetic fine mapping of causal autoimmune disease variants
Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., Shoresh, N., Whitton, H., Ryan, R. J. H., Shishkin, A. A., et al. (2015) · Nature · doi:10.1038/nature13835 · Cited by 1,956
Self-citationPhenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861
chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data
Schep, A. N., Wu, B., Buenrostro, J. D., & Greenleaf, W. J. (2017) · Nature Methods · doi:10.1038/nmeth.4401 · Cited by 1,680
Self-citationTH-17 cells in the circle of immunity and autoimmunity
Bettelli, E., Oukka, M., & Kuchroo, V. K. (2007) · Nature Immunology · doi:10.1038/ni0407-345 · Cited by 1,520
Self-citationMultiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
International Multiple Sclerosis Genetics Consortium, Patsopoulos, N. A., Baranzini, S. E., Santaniello, A., Shoostari, P., Cotsapas, C., Wong, G., Beecham, A. H., James, T., Replogle, J., et al. (2019) · Science · doi:10.1126/science.aav7188 · Cited by 1,471
Self-citationArchR is a scalable software package for integrative single-cell chromatin accessibility analysis
Granja, J. M., Corces, M. R., Pierce, S. E., Bagdatli, S. T., Choudhry, H., Chang, H. Y., & Greenleaf, W. J. (2021) · Nature Genetics · doi:10.1038/s41588-021-00790-6 · Cited by 1,392
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Ghoreschi, K., Laurence, A., Yang, X.-P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, L., Davidson, T. S., Bouladoux, N., et al. (2010) · Nature · doi:10.1038/nature09447 · Cited by 1,388
Fate mapping of IL-17-producing T cells in inflammatory responses
Hirota, K., Duarte, J. H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D. J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011) · Nature Immunology · doi:10.1038/ni.1993 · Cited by 1,176
Induction and molecular signature of pathogenic TH17 cells
Lee, Y., Awasthi, A., Yosef, N., Quintana, F. J., Xiao, S., Peters, A., Wu, C., Kleinewietfeld, M., Kunder, S., Hafler, D. A., et al. (2012) · Nature Immunology · doi:10.1038/ni.2416 · Cited by 1,174
Self-citationA Validated Regulatory Network for Th17 Cell Specification
Ciofani, M., Madar, A., Galan, C., Sellars, M., Mace, K., Pauli, F., Agarwal, A., Huang, W., Parkurst, C. N., Muratet, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.09.016 · Cited by 1,160
Corces, M. R., Buenrostro, J. D., Wu, B., Greenside, P. G., Chan, S. M., Koenig, J. L., Snyder, M. P., Pritchard, J. K., Kundaje, A., Greenleaf, W. J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3646 · Cited by 1,151
Self-citationChromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
Ma, S., Zhang, B., LaFave, L. M., Earl, A. S., Chiang, Z., Hu, Y., Ding, J., Brack, A., Kartha, V. K., Tay, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.056 · Cited by 1,146
Self-citationLate Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053
Javierre, B. M., Burren, O. S., Wilder, S. P., Kreuzhuber, R., Hill, S. M., Sewitz, S., Cairns, J., Wingett, S. W., Várnai, C., Thiecke, M. J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.037 · Cited by 1,046
Th17 and regulatory T cells in mediating and restraining inflammation
Littman, D. R., & Rudensky, A. Y. (2010) · Cell · doi:10.1016/j.cell.2010.02.021 · Cited by 1,039
The epigenetic landscape of T cell exhaustion
Sen, D. R., Kaminski, J., Barnitz, R. A., Kurachi, M., Gerdemann, U., Yates, K. B., Tsao, H.-W., Godec, J., LaFleur, M. W., Brown, F. D., et al. (2016) · Science · doi:10.1126/science.aae0491 · Cited by 986
The IL-12 Family of Heterodimeric Cytokines
Trinchieri, G., Pflanz, S., & Kastelein, R. A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00296-6 · Cited by 944
Hu, X., & Ivashkiv, L. B. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.002 · Cited by 928
Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β
Zielinski, C. E., Mele, F., Aschenbrenner, D., Jarrossay, D., Ronchi, F., Gattorno, M., Monticelli, S., Lanzavecchia, A., & Sallusto, F. (2012) · Nature · doi:10.1038/nature10957 · Cited by 919
Self-citationMurai, M., Turovskaya, O., Kim, G., Madan, R., Karp, C. L., Cheroutre, H., & Kronenberg, M. (2009) · Nature Immunology · doi:10.1038/ni.1791 · Cited by 885
Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression
Schmiedel, B. J., Singh, D., Madrigal, A., Valdovino-Gonzalez, A. G., White, B. M., Zapardiel-Gonzalo, J., Ha, B., Altay, G., Greenbaum, J. A., McVicker, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.022 · Cited by 867
Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation
Gagliani, N., Vesely, M. C. A., Iseppon, A., Brockmann, L., Xu, H. Y., Palm, N. W., de Zoete, M. R., Licona-Limón, P., Paiva, R., Ching, T. H., et al. (2015) · Nature · doi:10.1038/nature14452 · Cited by 830
Bettelli, E., Pagany, M., Weiner, H. L., Linington, C., Sobel, R. A., & Kuchroo, V. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021603 · Cited by 828
Self-citationSystems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4
Gilchrist, M., Thórsson, V., Li, B., Rust, A. G., Korb, M., Kennedy, K., Hai, T., Bolouri, H., & Aderem, A. A. (2006) · Nature · doi:10.1038/nature04768 · Cited by 810
Dynamic regulatory network controlling TH17 cell differentiation
Yosef, N., Shalek, A. K., Gaublomme, J. T., Jin, H., Lee, Y., Awasthi, A., Wu, C., Karwacz, K., Xiao, S., Jorgolli, M., et al. (2013) · Nature · doi:10.1038/nature11981 · Cited by 682
Self-citationHudson, W. H., Gensheimer, J., Hashimoto, M., Wieland, A., Valanparambil, R. M., Li, P., Lin, J.-X., Konieczny, B. T., Im, S. J., Freeman, G. J., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.11.002 · Cited by 656
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells
Kurtulus, S., Madi, A., Escobar, G., Klapholz, M., Nyman, J., Christian, E., Pawlak, M., Dionne, D., Xia, J., Rozenblatt-Rosen, O., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.014 · Cited by 636
Self-citationSingle-cell genomics unveils critical regulators of Th17 cell pathogenicity
Gaublomme, J. T., Yosef, N., Lee, Y., Gertner, R. S., Yang, L. V., Wu, C., Pandolfi, P. P., Mak, T., Satija, R., Shalek, A. K., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.009 · Cited by 575
Self-citationPreferential recruitment of interferon‐γ–expressing T H 17 cells in multiple sclerosis
Kebir, H., Ifergan, I., Alvarez, J. I., Bernard, M., Poirier, J., Arbour, N., Duquette, P., & Prat, A. (2009) · Annals of Neurology · doi:10.1002/ana.21748 · Cited by 551
Metabolic modeling of single Th17 cells reveals regulators of autoimmunity
Wagner, A., Wang, C., Fessler, J., DeTomaso, D., Avila-Pacheco, J., Kaminski, J., Zaghouani, S., Christian, E., Thakore, P., Schellhaass, B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.045 · Cited by 524
Self-citationElyaman, W., Bradshaw, E. M., Uyttenhove, C., Dardalhon, V., Awasthi, A., Imitola, J., Bettelli, E., Oukka, M., van Snick, J., Renauld, J.-C., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812530106 · Cited by 498
Self-citationNardo, D. D., Labzin, L. I., Kono, H., Seki, R., Schmidt, S. V., Beyer, M., Xu, D., Zimmer, S., Lahrmann, C., Schildberg, F. A., et al. (2013) · Nature Immunology · doi:10.1038/ni.2784 · Cited by 477
Frontline: Neuropilin‐1: a surface marker of regulatory T cells
Bruder, D., Probst-Kepper, M., Westendorf, A., Geffers, R., Beissert, S., Loser, K., von Boehmer, H., Buer, J., & Hansen, W. (2004) · European Journal of Immunology · doi:10.1002/eji.200324799 · Cited by 475
Herndler‐Brandstetter, D., Ishigame, H., Shinnakasu, R., Plajer, V., Stecher, C., Zhao, J., Lietzenmayer, M., Kroehling, L., Takumi, A., Kometani, K., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.015 · Cited by 457
cisTopic: cis-regulatory topic modeling on single-cell ATAC-seq data
Bravo González-Blas, C., Minnoye, L., Papasokrati, D., Aibar, S., Hulselmans, G., Christiaens, V., Davie, K., Wouters, J., & Aerts, S. (2019) · Nature Methods · doi:10.1038/s41592-019-0367-1 · Cited by 456
Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment
Nistala, K., Adams, S., Cambrook, H., Ursu, S., Olivito, B., de Jager, W., Evans, J. G., Cimaz, R., Bajaj-Elliott, M., & Wedderburn, L. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003852107 · Cited by 443
Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis
Harbour, S. N., Maynard, C. L., Zindl, C. L., Schoeb, T. R., & Weaver, C. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415675112 · Cited by 427
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells
Singer, M., Wang, C., Cong, L., Marjanovic, N. D., Kowalczyk, M. S., Zhang, H., Nyman, J., Sakuishi, K., Kurtuluş, S., Gennert, D. G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.052 · Cited by 422
Self-citationEssentials of Th17 cell commitment and plasticity
Muranski, P. J., & Restifo, N. P. (2013) · Blood · doi:10.1182/blood-2012-09-378653 · Cited by 421
The dichotomous nature of T helper 17 cells
Stockinger, B., & Omenetti, S. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.50 · Cited by 419
BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
Roychoudhuri, R., Hirahara, K., Mousavi, K., Clever, D. C., Klebanoff, C. A., Bonelli, M. M., Sciumè, G., Zare, H., Vahedi, G., Dema, B., et al. (2013) · Nature · doi:10.1038/nature12199 · Cited by 412
NF‐κB: roles and regulation in different CD 4+ T‐cell subsets
Oh, H., & Ghosh, S. (2013) · Immunological Reviews · doi:10.1111/imr.12033 · Cited by 408
CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity
Wang, C., Yosef, N., Gaublomme, J. T., Wu, C., Lee, Y., Clish, C. B., Kaminski, J., Xiao, S., zu Hörste, G. M., Pawlak, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.068 · Cited by 405
Self-citationIL-9 as a mediator of Th17-driven inflammatory disease
Nowak, E. C., Weaver, C. T., Turner, H., Begum-Haque, S., Becher, B., Schreiner, B., Coyle, A. J., Kasper, L. H., & Noelle, R. J. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20090246 · Cited by 393
Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells
Heink, S., Yogev, N., Garbers, C., Herwerth, M., Aly, L., Gasperi, C., Husterer, V., Croxford, A. L., Möller-Hackbarth, K., Bartsch, H. S., et al. (2017) · Nature Immunology · doi:10.1038/ni.3632 · Cited by 386
Martín‐Orozco, N., Chung, Y., Chang, S. H., Wang, Y., & Dong, C. (2009) · European Journal of Immunology · doi:10.1002/eji.200838475 · Cited by 370
Super-enhancers delineate disease-associated regulatory nodes in T cells
Vahedi, G., Kanno, Y., Furumoto, Y., Jiang, K., Parker, S. C. J., Erdos, M. R., Davis, S. R., Roychoudhuri, R., Restifo, N. P., Gadina, M., et al. (2015) · Nature · doi:10.1038/nature14154 · Cited by 369
Wei, L., Vahedi, G., Sun, H., Watford, W. T., Takatori, H., Ramos, H. L., Takahashi, H., Liang, J. Z., Gutierrez-Cruz, G., Zang, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.003 · Cited by 332
BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers
Roychoudhuri, R., Clever, D. C., Li, P., Wakabayashi, Y., Quinn, K. M., Klebanoff, C. A., Ji, Y., Sukumar, M., Eil, R. L., Yu, Z., et al. (2016) · Nature Immunology · doi:10.1038/ni.3441 · Cited by 317
The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells
Omenetti, S., Bussi, C., Metidji, A., Iseppon, A., Lee, S., Tolaini, M., Li, Y., Kelly, G., Chakravarty, P., Shoaie, S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.05.004 · Cited by 317
Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes
Chu, V. T., Weber, T., Graf, R., Sommermann, T. G., Petsch, K., Sack, U., Volchkov, P., Rajewsky, K., & Kühn, R. (2016) · BMC Biotechnology · doi:10.1186/s12896-016-0234-4 · Cited by 312
GPR15-Mediated Homing Controls Immune Homeostasis in the Large Intestine Mucosa
Kim, S. V., Xiang, W., Kwak, C., Yang, Y., Lin, X., Ota, M., Sarpel, U., Rifkin, D. B., Xu, R., & Littman, D. R. (2013) · Science · doi:10.1126/science.1237013 · Cited by 306
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286
Self-citationStem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Schnell, A., Huang, L., Singer, M., Singaraju, A., Barilla, R. M., Regan, B. M. L., Bollhagen, A., Thakore, P. I., Dionne, D., Delorey, T. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.018 · Cited by 268
Self-citationTh17 Cytokines and the Gut Mucosal Barrier
Blaschitz, C., & Raffatellu, M. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9368-7 · Cited by 258
Cumulus provides cloud-based data analysis for large-scale single-cell and single-nucleus RNA-seq
Li, B., Gould, J., Yang, Y., Sarkizova, S., Tabaka, M., Ashenberg, O., Rosen, Y., Slyper, M., Kowalczyk, M. S., Villani, A., et al. (2020) · Nature Methods · doi:10.1038/s41592-020-0905-x · Cited by 243
Self-citationMetabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity
Karmaus, P. W. F., Chen, X., Lim, S. A., Herrada, A. A., Nguyen, T.-L. M., Xu, B., Dhungana, Y., Rankin, S., Chen, W., Rosencrance, C., et al. (2019) · Nature · doi:10.1038/s41586-018-0806-7 · Cited by 215 · cited 1×
“Moreover, recent studies demonstrated an important role for BACH2 in the generation of stem-like CD8 + T cells 43,49 , and npT H 17 cells were shown to share multiple properties with stem-like CD8 + T cells, including a shared expression profile 9,13,45,61 .”
The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation
Ng, S. S., Rivera, F. D. L., Yan, J., Corvino, D., Das, I., Zhang, P., Kuns, R. D., Chauhan, S. B., Hou, J., Li, X.-Y., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0758-6 · Cited by 212
Ets-1 is a negative regulator of Th17 differentiation
Moisan, J., Grenningloh, R., Bettelli, E., Oukka, M., & Ho, I. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070994 · Cited by 205
Th17 cells in primary Sjögren's syndrome: Pathogenicity and plasticity
Verstappen, G. M. P. J., Corneth, O. B. J., Bootsma, H., & Kroese, F. G. M. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.11.003 · Cited by 204
Henriksson, J., Chen, X. X., Gomes, T., Ullah, U., Meyer, K. B., Miragaia, R. J., Duddy, G., Pramanik, J., Yusa, K., Lahesmaa, R., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.044 · Cited by 198
BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells
Yao, C., Lou, G., Sun, H., Zhu, Z., Sun, Y. E., Chen, Z., Chauss, D., Moseman, E. A., Cheng, J., D’Antonio, M. A., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00868-7 · Cited by 196
Eller, K., Wolf, D. G. F., Huber, J., Metz, M., Mayer, G. J., McKenzie, A. N. J., Maurer, M., Rosenkranz, A. R., & Wolf, A. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001183 · Cited by 187
Lin, C., Bradstreet, T. R., Schwarzkopf, E. A., Sim, J. E., Carrero, J. A., Chou, C., Cook, L. E., Egawa, T., Taneja, R., MURPHY, K. M. M., et al. (2014) · Nature Communications · doi:10.1038/ncomms4551 · Cited by 181
Molecular diversification of regulatory T cells in nonlymphoid tissues
DiSpirito, J. R., Zemmour, D., Ramanan, D., Cho, J., Žilionis, R., Klein, A. M., Benoist, C. O., & Mathis, D. J. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat5861 · Cited by 165
Aronica, M. A., Mora, A. L., Mitchell, D. B., Finn, P. W., Johnson, J. E., Sheller, J. R., & Boothby, M. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.9.5116 · Cited by 160
BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency
Afzali, B., Grönholm, J., Vandrovcová, J., O'Brien, C., Sun, H., Vanderleyden, I., Davis, F. P., Khoder, A., Zhang, Y., Hegazy, A. N., et al. (2017) · Nature Immunology · doi:10.1038/ni.3753 · Cited by 154
Oct transcription factors in development and stem cells: insights and mechanisms
Tantin, D. R. (2013) · Development · doi:10.1242/dev.095927 · Cited by 147
JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation
Carr, T. M., Wheaton, J. D., Houtz, G. M., & Ciofani, M. (2017) · Nature Communications · doi:10.1038/s41467-017-00380-3 · Cited by 146
dos Santos, A. C., Barsante, M. M., Arantes, R. M. E., Bernard, C. C. A., Teixeira, M. M., & Tavares, J. C. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.01.020 · Cited by 138
BACH transcription factors in innate and adaptive immunity
Igarashi, K., Kurosaki, T., & Roychoudhuri, R. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.26 · Cited by 132
RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression
zu Hörste, G. M., Wu, C., Wang, C., Cong, L., Pawlak, M., Lee, Y., Elyaman, W., Xiao, S., Regev, A., & Kuchroo, V. K. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.088 · Cited by 118
Self-citationAntibodies to the IL-12 Receptor β2 Chain Mark Human Th1 But Not Th2 Cells In Vitro and In Vivo
Rogge, L., Papi, A. A., Presky, D. H., Biffi, M., Minetti, L. J., Miotto, D., Agostini, C., Semenzato, G., Fabbri, L. M., & Sinigaglia, F. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3926 · Cited by 118
Kim, E. H., Gasper, D. J., Lee, S. H., Plisch, E. H., Svaren, J. P., & Suresh, M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1302378 · Cited by 116
Essential Roles of SATB1 in Specifying T Lymphocyte Subsets
Kakugawa, K., Kojo, S., Tanaka, H., Seo, W., Endo, T. A., Kitagawa, Y., Muroi, S., Tenno, M., Yasmin, N., Kohwi, Y., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.038 · Cited by 103
IL-1–induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation
Lin, C., Bradstreet, T. R., Schwarzkopf, E. A., Jarjour, N. N., Chou, C., Archambault, A. S., Sim, J. E., Zinselmeyer, B. H., Carrero, J. A., Wu, G. F., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20150568 · Cited by 102
An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells
Aschenbrenner, D., Foglierini, M., Jarrossay, D., Hu, D., Weiner, H. L., Kuchroo, V. K., Lanzavecchia, A., Notarbartolo, S., & Sallusto, F. (2018) · Nature Immunology · doi:10.1038/s41590-018-0200-5 · Cited by 101
Self-citationFragale, A., Gabriele, L., Stellacci, E., Borghi, P., Perrotti, E., Ilari, R., Lanciotti, A., Remoli, A. L., Venditti, M., Belardelli, F., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.3.1673 · Cited by 93
Zhang, H., Madi, A., Yosef, N., Chihara, N., Awasthi, A., Pot, C., Lambden, C., Srivastava, A., Burkett, P. R., Nyman, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108433 · Cited by 91
Self-citationPorter, C. M., & Clipstone, N. A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.10.4936 · Cited by 89
Reinert‐Hartwall, L., Honkanen, J. K., Salo, H. M., Nieminen, J. K., Luopajärvi, K., Härkönen, T., Veijola, R., Simell, O., Ilonen, J., Peet, A., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401653 · Cited by 86
Paroni, M., Maltese, V., De Simone, M., Ranzani, V., Larghi, P., Fenoglio, C., Pietroboni, A. M., De Riz, M. A., Crosti, M. C., Maglie, S., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.11.045 · Cited by 77
Grant, F. M., Yang, J., Nasrallah, R., Clarke, J. D., Sadiyah, F., Whiteside, S. K., Imianowski, C. J., Kuo, P., Vardaka, P., Todorov, T. Z., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190711 · Cited by 77
zu Hörste, G. M., Przybylski, D., Schramm, M. A., Wang, C., Schnell, A., Lee, Y., Sobel, R. A., Regev, A., & Kuchroo, V. K. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.008 · Cited by 74
Self-citationEomes controls the development of Th17‐derived (non‐classic) Th1 cells during chronic inflammation
Mazzoni, A., Maggi, L., Siracusa, F., Ramazzotti, M., Rossi, M. C., Santarlasci, V., Montaini, G., Capone, M., Rossettini, B., Palma, R. D., et al. (2018) · European Journal of Immunology · doi:10.1002/eji.201847677 · Cited by 74
Johnson, R. M., Kerr, M. S., & Slaven, J. E. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102764 · Cited by 71
Biological and clinical significance of T helper 17 cell plasticity
Mazzoni, A., Maggi, L., Liotta, F., Cosmi, L., & Annunziato, F. (2019) · Immunology · doi:10.1111/imm.13124 · Cited by 68
Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation
Xiao, S., Bod, L., Pochet, N. L. M. M., Kota, S. B., Hu, D., Madi, A., Kilpatrick, J., Shi, J., Ho, A. W., Zhang, H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107892 · Cited by 68
Self-citationMouri, K., Guo, M. H., de Boer, C. G., Lissner, M. M., Harten, I. A., Newby, G. A., DeBerg, H. A., Platt, W. F., Gentili, M., Liu, D. R., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01056-5 · Cited by 67
Hiltensperger, M., Beltrán, E., Kant, R., Tyystjärvi, S., Lepennetier, G., Moreno, H. D., Bauer, I., Grassmann, S. A., Jarosch, S., Schober, K., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00948-8 · Cited by 65
Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity
Kishi, Y., Kondo, T., Xiao, S., Yosef, N., Gaublomme, J. T., Wu, C., Wang, C., Chihara, N., Regev, A., Joller, N., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151118 · Cited by 61
Self-citationTortola, L., Jacobs, A., Pohlmeier, L. M., Obermair, F.-J., Ampenberger, F., Bodenmiller, B., & Köpf, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.001 · Cited by 58
Duffus, K., Yarwood, A., Bowes, J., Orozco, G., Viatte, S., Diogo, D., Hocking, L. J., Steer, S. E., Wordsworth, P., Wilson, A. G., et al. (2013) · Arthritis & Rheumatism · doi:10.1002/art.38183 · Cited by 57
Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling
Pawlak, M., DeTomaso, D., Schnell, A., Meyer zu Horste, G., Lee, Y., Nyman, J., Dionne, D., Regan, B. M. L., Singh, V., Delorey, T., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.007 · Cited by 49
Self-citationYang, L., Chen, S., Zhao, Q., Sun, Y., & Nie, H. (2019) · Mediators of Inflammation · doi:10.1155/2019/2609737 · Cited by 47
Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression
Filén, S., Ylikoski, E. K., Tripathi, S. K., West, A., Björkman, M. L., Nyström, J. H., Ahlfors, H., Coffey, E. T., Rao, K. V. S., Rasool, O., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903106 · Cited by 45
Nr4a1 plays a crucial modulatory role in Th1/Th17 cell responses and CNS autoimmunity
Wang, L., Zhang, Y., Li, X., Zhang, M., Zhu, L. D., Zhang, G., & Xu, Y. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.09.015 · Cited by 42
Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell, A., Huang, L., Regan, B. M. L., Singh, V., Vonficht, D., Bollhagen, A., Wang, M., Hou, Y., Bod, L., Sobel, R. A., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01645-4 · Cited by 39
Self-citationDefining the functional states of Th17 cells
Lee, Y., & Kuchroo, V. K. (2015) · F1000Research · doi:10.12688/f1000research.6116.1 · Cited by 32
Self-citationAnti-inflammatory genes associated with multiple sclerosis: A gene expression study
Perga, S., Montarolo, F., Martire, S., Berchialla, P., Malucchi, S., & Bertolotto, A. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.01.004 · Cited by 24
Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets
Guo, M. H., Sama, P., LaBarre, B. A., Lokhande, H. A., Balibalos, J., Chu, C., Du, X., Kheradpour, P., Kim, C. C., Oniskey, T. K., et al. (2022) · Genome biology · doi:10.1186/s13059-022-02694-y · Cited by 23
Self-citationStem‐like T cells in cancer and autoimmunity
Schnell, A. (2024) · Immunological Reviews · doi:10.1111/imr.13356 · Cited by 22
Self-citationZheng, S., Hedl, M., & Abraham, C. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402808 · Cited by 21
Research works printed but not linked: 1
- 10.1186/PREACCEPT-8897612761307401 · DOI
Cited by
Sorted by citations
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286
Self-citationTh17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75
Hu, Y., Yang, Y., Li, Y., Zhang, Q., Zhang, W., Jia, J., Han, Z., & Wang, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1651063 · Cited by 74
IL-17: Balancing Protective Immunity and Pathogenesis
Sun, L., Wang, L., Moore, B. B., Zhang, S., Xiao, P., Decker, A. M., & Wang, H. (2023) · Journal of Immunology Research · doi:10.1155/2023/3360310 · Cited by 66
Th17 Cells, Glucocorticoid Resistance, and Depression
Khantakova, J. N., Mutovina, A., Ayriyants, K. A., & Bondar, N. P. (2023) · Cells · doi:10.3390/cells12232749 · Cited by 36
Metadata
- Authors
- Thakore, P. I., Schnell, A., Zhao, M., Huang, L., Hou, Y., Christian, E., Zaghouani, S., Wang, C., Singh, V., Ma, S., Sankar, V., Notarbartolo, S., Buenrostro, J. D., Sallusto, F., Patsopoulos, N. A., Rozenblatt-Rosen, O., Kuchroo, V. K., & Regev, A.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- ETH Zurich (CH)
- Corresponding author
- Kuchroo, Vijay K.
- Regev, Aviv
- ORCID
- Venue
- Nature Immunology
- Publisher
- openRxiv
- Published
- 2022-02-26
- Volume
- 25
- Issue
- 8
- Pages
- 1395-1410
- ISSN
- 1529-2908 (ISSN-L)
- OpenAlex
- W4400657378
- Cited by
- 57
- References
- 122
- Citations by year
- 2026: 24 · 2025: 24 · 2024: 4 · 2023: 5
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services (R01AI144166, R01NS30843, R01NS045937)
- National Institutes of Health (R01NS30843)
- National Institute of Allergy and Infectious Diseases (R01AI144166)
- National Institute of Neurological Disorders and Stroke (R01NS030843, R01NS045937)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- BACH2, Th17 cells, chromatin accessibility, regulatory T cells, transcriptional regulatory networks, IL-17, multiple sclerosis, autoimmunity, epigenetic regulation, cellular heterogeneity
- MeSH terms
- Animals, Chromatin, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Mice, Knockout, Th1 Cells, T-Lymphocytes, Regulatory, Basic-Leucine Zipper Transcription Factors, Mice, Th17 Cells, Single-Cell Analysis
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
