The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17–producing T cells
Open accessAbstract
The molecular mechanisms underlying the differentiation of interleukin 17–producing T helper cells (TH-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors RORγt and Runx1. Runx1 influenced TH-17 differentiation by inducing RORγt expression and by binding to and acting together with RORγt during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on TH-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORγt regulates TH-17 differentiation.
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.
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
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
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
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087
IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K., & Iwakura, Y. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.1.566 · Cited by 1,536
Essential autocrine regulation by IL-21 in the generation of inflammatory T cells
Nurieva, R., Yang, X. O., Martinez, G., Zhang, Y., Panopoulos, A. D., Ma, L., Schluns, K., Tian, Q., Watowich, S. S., Jetten, A. M., et al. (2007) · Nature · doi:10.1038/nature05969 · Cited by 1,466
Akimzhanov, A. M., Yang, X. O., & Dong, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c600322200 · Cited by 302
(2008) · Advances in Cancer Research · doi:10.1016/s0065-230x(07)99002-8 · Cited by 203
Cited by
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
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452
Psoriasis Pathogenesis and Treatment
Rendon, A., & Schäkel, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061475 · Cited by 2,064
Plasticity of CD4+ T Cell Lineage Differentiation
Zhou, L., Chong, M. M. W., & Littman, D. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.001 · Cited by 1,551
Interleukin-17 and Type 17 Helper T Cells
Miossec, P., Korn, T., & Kuchroo, V. K. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0707449 · Cited by 1,409
CD4 + T Cells: Differentiation and Functions
Luckheeram, R. V., Zhou, R., Verma, A. D., & Xia, B. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/925135 · Cited by 1,381
A 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
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
Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,014
Jetten, A. M. (2009) · Nuclear Receptor Signaling · doi:10.1621/nrs.07003 · Cited by 673
The AP-1 transcription factor Batf controls TH17 differentiation
Schraml, B. U., Hildner, K., Ise, W., Lee, W.-L., Smith, W. A.-E., Solomon, B., Sahota, G., Sim, J., Mukasa, R., Cemerski, S., et al. (2009) · Nature · doi:10.1038/nature08114 · Cited by 630
Ribot, J. C., deBarros, A., Pang, D. J., Neves, J. F., Peperzak, V., Roberts, S. J., Girardi, M., Borst, J., Hayday, A. C., Pennington, D. J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1717 · Cited by 628
The regulation of immune tolerance by FOXP3
Lu, L., Barbi, J., & Pan, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.75 · Cited by 580
Peripheral CD4+ T‐cell differentiation regulated by networks of cytokines and transcription factors
Zhu, J., & Paul, W. E. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00951.x · Cited by 579
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand
Solt, L. A., Kumar, N., Nuhant, P., Wang, Y., Lauer, J. L., Liu, J., Istrate, M. A., Kamenecka, T. M., Roush, W. R., Vidović, D., et al. (2011) · Nature · doi:10.1038/nature10075 · Cited by 508
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489
Joshi, S., Pantalena, L.-C., Liu, X. K., Gaffen, S. L., Liu, H., Rohowsky-Kochan, C., Ichiyama, K., Yoshimura, A., Steinman, L., Christakos, S., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05020-11 · Cited by 458
The RUNX family: developmental regulators in cancer
Ito, Y., Bae, S.-C., & Chuang, L. S. H. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3877 · Cited by 399
Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective
Weaver, C. T., & Hatton, R. D. (2009) · Nature Reviews Immunology · doi:10.1038/nri2660 · Cited by 395
Essentials of Th17 cell commitment and plasticity
Muranski, P., & Restifo, N. P. (2013) · Blood · doi:10.1182/blood-2012-09-378653 · Cited by 383
Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O'Shea, J. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075058 · Cited by 342
“T-bet also inhibits the function of Gata3 and Rorc, thereby antagonizing Th2 and Th17 differentiation.”
BackgroundInfluentialLoser, K., Vogl, T., Voskort, M., Lueken, A., Kupas, V., Nacken, W., Klenner, L., Kuhn, A., Foell, D., Sorokin, L., et al. (2010) · Nature Medicine · doi:10.1038/nm.2150 · Cited by 296
Genomic views of STAT function in CD4+ T helper cell differentiation
O'Shea, J. J., Lahesmaa, R., Vahedi, G., Laurence, A., & Kanno, Y. (2011) · Nature Reviews Immunology · doi:10.1038/nri2958 · Cited by 295
Interleukin-23/Th17 pathways and inflammatory bowel disease
Abraham, C., & Cho, J. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20894 · Cited by 289
Reis, B. S., Rogoz, A., Costa-Pinto, F. A., Taniuchi, I., & Mucida, D. (2013) · Nature Immunology · doi:10.1038/ni.2518 · Cited by 279
IκBζ regulates TH17 development by cooperating with ROR nuclear receptors
Okamoto, K., Iwai, Y., Oh-hora, M., Yamamoto, M., Morio, T., Aoki, K., Ohya, K., Jetten, A. M., Akira, S., Muta, T., et al. (2010) · Nature · doi:10.1038/nature08922 · Cited by 265
Kuang, D.-M., Peng, C., Zhao, Q., Wu, Y., Chen, M.-S., & Zheng, L. (2010) · Hepatology · doi:10.1002/hep.23291 · Cited by 263
Th17 cells: from precursors to players in inflammation and infection
Awasthi, A., & Kuchroo, V. K. (2009) · International Immunology · doi:10.1093/intimm/dxp021 · Cited by 241
Chen, L., Sun, M., Wu, W., Yang, W., Huang, X., Xiao, Y., Ma, C., Xu, L., Yao, S., Liu, Z., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz046 · Cited by 231
NFAT pulls the strings during CD4+ T helper cell effector functions
Hermann-Kleiter, N., & Baier, G. (2010) · Blood · doi:10.1182/blood-2009-10-233585 · Cited by 218
RUNX transcription factors: orchestrators of development
Mevel, R., Draper, J. E., Lie-a-Ling, M., Kouskoff, V., & Lacaud, G. (2019) · Development · doi:10.1242/dev.148296 · Cited by 211
Ono, M. (2020) · Immunology · doi:10.1111/imm.13178 · Cited by 187
REV-ERBα Regulates TH17 Cell Development and Autoimmunity
Amir, M., Chaudhari, S., Wang, R., Campbell, S., Mosure, S. A., Chopp, L. B., Lu, Q., Shang, J., Pelletier, O. B., He, Y., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.101 · Cited by 117
Bhaumik, S., & Basu, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00254 · Cited by 119
The Inhibitory Receptor BTLA Controls γδ T Cell Homeostasis and Inflammatory Responses
Bekiaris, V., Šedý, J. R., Macauley, M. G., Rhode-Kurnow, A., & Ware, C. F. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.017 · Cited by 95
Protein phosphatase 2A enables expression of interleukin 17 (IL-17) through chromatin remodeling
Apostolidis, S. A., Rauen, T., Hedrich, C. M., Tsokos, G. C., & Crispín, J. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.483743 · Cited by 91
Transcription factor interplay in T helper cell differentiation
Evans, C. M., & Jenner, R. G. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/elt025 · Cited by 91
Signal transduction and Th17 cell differentiation
O'Shea, J. J., Steward-Tharp, S. M., Laurence, A., Watford, W. T., Wei, L., Adamson, A. S., & Fan, S. (2009) · Microbes and Infection · doi:10.1016/j.micinf.2009.04.007 · Cited by 73
Th17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75
T cell receptor/CARMA1/NF-κB signaling controls T-helper (Th) 17 differentiation
Molinero, L. L., Cubre, A., Mora-Solano, C., Wang, Y., & Alegre, M.-L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1204557109 · Cited by 61
RUNX transcription factors: association with pediatric asthma and modulated by maternal smoking
Haley, K. J., Lasky-Su, J., Manoli, S. E., Smith, L. A., Shahsafaei, A., Weiss, S. T., & Tantisira, K. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00348.2010 · Cited by 58
Update on the role of Interleukin 17 in rheumatologic autoimmune diseases
Konya, C., Paz, Z., Apostolidis, S. A., & Tsokos, G. C. (2015) · Cytokine · doi:10.1016/j.cyto.2015.01.003 · Cited by 35
Identification of Acvr2a as a Th17 Cell-Specific Gene Induced during Th17 Differentiation
IHN, H.-J., KIM, D. H., OH, S.-S., MOON, C., CHUNG, J. W., SONG, H., & KIM, K. D. (2011) · Bioscience, Biotechnology, and Biochemistry · doi:10.1271/bbb.110436 · Cited by 9
Metadata
- Authors
- Zhang, F., Meng, G., & Strober, W.
- Venue
- Nature Immunology
- Published
- 2008-10-12
- Volume
- 9
- Issue
- 11
- Pages
- 1297-1306
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2154728251
- Cited by
- 500
- References
- 8
- FWCI
- 17.44
- Type
- journal article
- Language
- en
- Open access
- green
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.