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Individual intestinal symbionts induce a distinct population of RORγ + regulatory T cells
Open accessAbstract
Gut microbes make T cells keep the peace: Our guts harbor trillions of microbial inhabitants, some of which regulate the types of immune cells that are present in the gut. For instance, Clostridium species of bacteria induce a type of T cell that promotes tolerance between the host and its microbial contents. Ohnmacht et al. and Sefik et al. characterized a population of gut regulatory T cells in mice, which required gut microbiota to survive. Multiple bacterial species of the microbiota could induce transcription factor–expressing regulatory T cells that helped maintain immune homeostasis. Mice engineered to lack these transcription factors exhibited enhanced susceptibility to colonic inflammation and had elevated amounts of proinflammatory molecules associated with allergies (see the Perspective by Hegazy and Powrie). Science , this issue pp. 989 and 993
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“Yet, Helios, Nrp-1 or ROR-γt are widely accepted for the discrimination of tTreg and pTreg cells under homeostatic conditions [364-366, 437-440].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [437]
Experimental — accuracy not yet measuredIn the citing paper
“In addition, the gut microbiome regulates the activity of retinoic acid receptor-related orphan receptor gamma-positive (RORγ+) Treg cells, dysregulation of which can lead to diseases such as colitis, food allergy, and colon cancer.622,701–704”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [701]
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Citations
Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models
Stamatakis, A. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl446 · Cited by 15,582
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
The Pfam Protein Families Database
Bateman, A. G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.276 · Cited by 14,075
Prodigal: prokaryotic gene recognition and translation initiation site identification
Hyatt, D., Chen, G.-L., LoCascio, P. F., Land, M., Larimer, F. W., & Hauser, L. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-119 · Cited by 12,692
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
Krogh, A., Larsson, B., von Heijne, G., & Sonnhammer, E. L. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4315 · Cited by 12,654
Conesa, A., Götz, S., Garcia-Gomez, J. M., Terol, J., Talón, M., & Robles, M. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti610 · Cited by 11,417
tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence
Lowe, T. M., & Eddy, S. R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.5.955 · Cited by 11,200
SignalP 4.0: discriminating signal peptides from transmembrane regions
Petersen, T. N., Brunak, S., von Heijne, G., & Nielsen, H. (2011) · Nature Methods · doi:10.1038/nmeth.1701 · Cited by 8,847
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
RNAmmer: consistent and rapid annotation of ribosomal RNA genes
Lagesen, K., Hallin, P., Rødland, E., Stærfeldt, H., Rognes, T., & Ussery, D. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm160 · Cited by 5,965
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413
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
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
A genomic perspective on protein families.
Tatusov, R., Koonin, E., & Lipman, D. (1997) · Science · doi:10.1126/science.278.5338.631 · Cited by 3,777
Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. (2013) · Nature · doi:10.1038/nature12331 · Cited by 2,872
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145
Self-citationReich, M. M., Liefeld, T., Gould, J., Lerner, J., Tamayo, P., & Mesirov, J. P. (2006) · Nature Genetics · doi:10.1038/ng0506-500 · Cited by 2,053
Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007) · Science · doi:10.1126/science.1145697 · Cited by 1,982
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,928
The Pfam protein families database
Finn, R. D., Tate, J. G., Mistry, J., Coggill, P. C., Sammut, S., Hotz, H.-R., Ceric, G., Forslund, S. K., Eddy, S. R., Sonnhammer, E. L. L., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm960 · Cited by 1,847
Innate IL-17-producing cells: the sentinels of the immune system
Cua, D. J., & Tato, C. M. (2010) · Nature reviews. Immunology · doi:10.1038/nri2800 · Cited by 1,640
Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W. R., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.017 · Cited by 1,586
Dillies, M., Rau, A., Aubert, J., Hennequet‐Antier, C., Jeanmougin, M., Servant, N., Keime, C., Marot, G., Castel, D., Estellé, J., et al. (2012) · Briefings in Bioinformatics · doi:10.1093/bib/bbs046 · Cited by 1,363
A Special Population of Regulatory T Cells Potentiates Muscle Repair
Burzyn, D., Kuswanto, W., Kolodin, D., Shadrach, J. L., Cerletti, M., Jang, Y., Sefik, E., Tan, T. G., Wagers, A. J., Benoist, C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.054 · Cited by 1,234
Self-citationMolecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Yang, X. O., Nurieva, R., Martínez, G., Kang, H. S., Chung, Y., Pappu, B. P., Shah, B., Chang, S. H., Schluns, K. S., Watowich, S. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.007 · Cited by 1,169
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S. E., Benoist, C., & Mathis, D. (2012) · Nature · doi:10.1038/nature11132 · Cited by 1,143
Self-citationPeripheral education of the immune system by colonic commensal microbiota
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C.-W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C.-S. (2011) · Nature · doi:10.1038/nature10434 · Cited by 1,034
The alarmin IL-33 promotes regulatory T-cell function in the intestine
Schiering, C., Krausgruber, T., Chomka, A., Fröhlich, A., Adelmann, K., Wohlfert, E. A., Pott, J., Griseri, T., Bollrath, J., Hegazy, A. N., et al. (2014) · Nature · doi:10.1038/nature13577 · Cited by 1,007
Eberl, G., Marmon, S., Sunshine, M. J., Rennert, P. D., Choi, Y., & Littman, D. R. (2003) · Nature Immunology · doi:10.1038/ni1022 · Cited by 986
Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses
Geuking, M. B., Cahenzli, J., Lawson, M. A. E., Ng, D. C. K., Slack, E., Hapfelmeier, S., McCoy, K. D., & Macpherson, A. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.021 · Cited by 840
Jetten, A. M. (2009) · Nuclear Receptor Signaling · doi:10.1621/nrs.07003 · Cited by 700
Natural history and evolutionary principles of gene duplication in fungi
Wapinski, I., Pfeffer, A., Friedman, N., & Regev, A. (2007) · Nature · doi:10.1038/nature06107 · Cited by 614
Induced CD4+Foxp3+Regulatory T Cells in Immune Tolerance
Bilate, A. M., & Lafaille, J. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075043 · Cited by 569
GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
Wohlfert, E. A., Grainger, J. R., Bouladoux, N., Konkel, J. E., Oldenhove, G., Ribeiro, C. H., Hall, J. A., Yagi, R., Naik, S., Bhairavabhotla, R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57456 · Cited by 556
TIGRFAMs: a protein family resource for the functional identification of proteins
Haft, D. H. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.41 · Cited by 495
Townsend, M. J., Fallon, P. G., Matthews, D. J., Jolin, H. E., & McKenzie, A. N. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.6.1069 · Cited by 482
Sawada, S. (1994) · Cell · doi:10.1016/0092-8674(94)90140-6 · Cited by 439
Phenotypic and functional characterization of mice that lack the type I receptor for IL-1.
Glaccum, M. B., Stocking, K., Charrier, K., Smith, J., Willis, C., Maliszewski, C., Livingston, D., Peschon, J., & Morrissey, P. (1997) · Journal of Immunology · doi:10.4049/jimmunol.159.7.3364 · Cited by 418
Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota
Cebula, A., Seweryn, M. T., Rempała, G. A., Pabla, S. S., McIndoe, R., Denning, T. L., Bry, L., Kraj, P. J., Kisielow, P., & Ignatowicz, L. (2013) · Nature · doi:10.1038/nature12079 · Cited by 392
Faith, J. J., Ahern, P. P., Ridaura, V. K., Cheng, J., & Gordon, J. I. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008051 · Cited by 373
Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells
Awasthi, A., Riol‐Blanco, L., Jäger, A., Korn, T., Pot, C., Galileos, G., Bettelli, E., Kuchroo, V. K., & Oukka, M. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900732 · Cited by 365
Regulatory T cells in nonlymphoid tissues
Burzyn, D., Benoist, C. O., & Mathis, D. J. (2013) · Nature Immunology · doi:10.1038/ni.2683 · Cited by 351
Self-citationXiao, S., Yosef, N., Yang, J., Wang, Y., Zhou, L., Zhu, C. Y., Wu, C., Baloglu, E., Schmidt, D. R., Ramesh, R., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.04.004 · Cited by 283
Self-citationDifferentiation of regulatory Foxp3 + T cells in the thymic cortex
Liston, A., Nutsch, K., Farr, A. G., Lund, J. M., Rasmussen, J. P., Koni, P. A., & Rudensky, A. Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801506105 · Cited by 238
IL-23 and Autoimmunity: New Insights into the Pathogenesis of Inflammatory Bowel Disease
Abraham, C., & Cho, J. H. (2008) · Annual Review of Medicine · doi:10.1146/annurev.med.60.051407.123757 · Cited by 169
Gonzalez, A., André‐Schmutz, I., Carnaud, C., Mathis, D. J., & Benoist, C. O. (2001) · Nature Immunology · doi:10.1038/ni738 · Cited by 155
Self-citationSkepner, J. E., Ramesh, R., Trocha, M., Schmidt, D. R., Baloglu, E., Lobera, M., Carlson, T. J., Hill, J. A., Orband‐Miller, L. A., Barnes, A. A., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302190 · Cited by 143
Self-citationAutomatic genome-wide reconstruction of phylogenetic gene trees
Wapinski, I., Pfeffer, A., Friedman, N., & Regev, A. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm193 · Cited by 136
EFICAz: a comprehensive approach for accurate genome-scale enzyme function inference
Tian, W., Arakaki, A. K., & Skolnick, J. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh956 · Cited by 106
Du, R., Zhao, H., Fan, Y. L., & Li, H. (2014) · Journal of Leukocyte Biology · doi:10.1189/jlb.1ru0114-010rr · Cited by 93
Lochner, M., Berard, M., Sawa, S., Hauer, S., Gaboriau‐Routhiau, V., Fernández, T. D., Snel, J., Bousso, P., Cerf–Bensussan, N., & Eberl, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001723 · Cited by 86
T‐cell selection and intestinal homeostasis
Ai, T. L., Solomon, B. D., & Hsieh, C. (2014) · Immunological Reviews · doi:10.1111/imr.12171 · Cited by 57
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Metadata
- Authors
- Sefik, E., Geva-Zatorsky, N., Oh, S., Konnikova, L., Zemmour, D., McGuire, A. M., Burzyn, D., Ortiz-Lopez, A., Lobera, M., Yang, J., Ghosh, S., Earl, A., Snapper, S. B., Jupp, R., Kasper, D., Mathis, D., & Benoist, C.
- Affiliations
- Harvard University (US)
- Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
- Brigham and Women's Hospital (US)
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
- Tempero Pharmaceuticals, a GSK Company, Cambridge, MA 02115, USA.
- Broad Institute (US)
- UCB Pharma (United Kingdom) (GB)
- Corresponding author
- Mathis, Diane
- Benoist, Christophe
- ORCID
- Venue
- Science
- Published
- 2015-08-28
- Volume
- 349
- Issue
- 6251
- Pages
- 993-997
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4700932
- OpenAlex
- W2143889757
- Cited by
- 879
- References
- 60
- Citations by year
- 2026: 54 · 2025: 76 · 2024: 83 · 2023: 96 · 2022: 98 · 2021: 91 · 2020: 90 · 2019: 86 · 2018: 78 · 2017: 69 · 2016: 56 · 2015: 2
- FWCI
- 33.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01-AI51530, R56-AI110630)
- European Molecular Biology Organization
- Human Frontier Science Program
- Helmsley Charitable Trust
- Boehringer Ingelheim Fonds
- J.P.B. Foundation
- UCB Pharma
- Center for Inflammatory Bowel Disease Treatment and Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- RORγ, regulatory T cells, Foxp3, gut microbiota, intestinal symbionts, Th17 cells, colonic inflammation, Th1/Th17 balance, transcriptional regulation, immune homeostasis
- MeSH terms
- Animals, Bacteria, Colitis, Ulcerative, Colon, Homeostasis, Humans, Intestinal Mucosa, Mice, Inbred C57BL, Symbiosis, Transcription, Genetic, T-Lymphocyte Subsets, Immunity, Mucosal, Bacteroidetes, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Transcriptome, Microbiota
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