The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells
Open accessAbstract
We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.
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In the citing paper
“Here, we report that in addition to its key role in Th17 cell induction (3, 4), there is an absolute requirement for persistent IL-6 signaling to maintain the Th17 genetic program, and thus Th17 cells.”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [3]
In the citing paper
“IL-6 together with TGFβ induces Th17 cells (Fig. 2) (164).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [164]
In the citing paper
“The produced IL-6 further induces Th17 cell differentiation through STAT3 in the presence of TGFβ, IL-1β and IL-23, all of which are rich in inflammatory lesions and tumor microenvironments (164, 166, 169–171, 174, 175).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [164]
In the citing paper
“Th17 cells were established as an independent T helper cell subset with the discovery of signature cytokines IL-17A, IL-17F, and IL-22, lineage-specific differentiation factors, and dedicated or “master” transcription factors”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [10]
In the citing paper
“In response to TGF-β in vitro as well as in vivo, many T cells co-express RORγt and Foxp3 (Veldhoen et al., 2006; Yang et al., 2008a).”
From Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1 (2011) · cites this paper as Veldhoen et al., 2006
Citations
Cites
Interleukin-10 and the Interleukin-10 Receptor
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.683 · Cited by 6,737
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,860
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099
A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment
Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., & Glimcher, L. H. (2000) · Cell · doi:10.1016/s0092-8674(00)80702-3 · Cited by 3,589
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K. P., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00070-4 · Cited by 2,819
Sakaguchi, S. (2005) · Nature Immunology · doi:10.1038/ni1178 · Cited by 2,669
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Harusato, A., Abo, H., Ngo, V. L., Yi, S. W., Mitsutake, K., Osuka, S., Kohlmeier, J. E., Li, J., Gewirtz, A. T., Nusrat, A., et al. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.21 · Cited by 104
Suryani, S., & Sutton, I. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.023 · Cited by 92
Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective
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Rao, D. A., Eid, R. E., Qin, L., Yi, T., Kirkiles-Smith, N. C., Tellides, G., & Pober, J. S. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081661 · Cited by 86
Maternal immune stimulation during pregnancy shapes the immunological phenotype of offspring
Mandal, M., Donnelly, R., Elkabes, S., Zhang, P., Davini, D., David, B. T., & Ponzio, N. M. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.04.012 · Cited by 81
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“It has been previously shown that TGF-b and IL-6 can promote the differentiation of naive CD4 cells to IL17–producing T cells (21).”
Chen, Y., Li, C., Weng, D., Song, L., Tang, W., Dai, W., Yu, Y., Liu, F., Zhao, M., Lu, C., et al. (2014) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.11.012 · Cited by 75
“In addition, the effect of IL-6 and TGF-β in Th17 cell induction was shown to be amplified when IL1β was used as a co-stimulator (Bettelli et al., 2006; Veldhoen et al., 2006).”
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Iwamura, C., & Nakayama, T. (2008) · Current Allergy and Asthma Reports · doi:10.1007/s11882-008-0003-0 · Cited by 76
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Chan, Y. R., Chen, K., Duncan, S. R., Lathrop, K. L., Latoche, J. D., Logar, A. J., Pociask, D. A., Wahlberg, B. J., Ray, P., Ray, A., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.05.036 · Cited by 73
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
Naseem, S., Hussain, T., & Manzoor, S. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.002 · Cited by 72
Zhang, Y., He, X., Wu, X., Lei, M., Wei, Z., Zhang, X., Wen, L., Xu, P., Li, S., & Qu, S. (2017) · Cell Death & Disease · doi:10.1038/cddis.2016.491 · Cited by 66
Galectin-3 Modulates Th17 Responses by Regulating Dendritic Cell Cytokines
Fermin Lee, A., Chen, H.-Y., Wan, L., Wu, S.-Y., Yu, J.-S., Huang, A. C., Miaw, S.-C., Hsu, D. K., Wu-Hsieh, B. A., & Liu, F.-T. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.06.017 · Cited by 63
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BackgroundInfluentialMurakami, M., & Hirano, T. (2011) · Frontiers in Immunology · doi:10.3389/fimmu.2011.00022 · Cited by 53
“…IFNγ, IL-4, and IL-17A, respectively (Mosmann and Coffman, 1989; Glimcher and Murphy, 2000; Cua et al., 2003; Harrington et al., 2005; Park et al., 2005; Veldhoen et al., 2006; Zhu et al., 2006; Bettelli et al., 2007; Nishihara et al., 2007) – may initiate and drive the progression of disease.”
The CREB/CRTC2 pathway modulates autoimmune disease by promoting Th17 differentiation
Hernandez, J. B., Chang, C., LeBlanc, M., Grimm, D., Le Lay, J., Kaestner, K. H., Zheng, Y., & Montminy, M. (2015) · Nature Communications · doi:10.1038/ncomms8216 · Cited by 53
Detection of IL-17 and IL-23 in Plasma Samples of Children with Autism
Enstrom, A., Onore, C., Hertz-Picc, I., Hansen, R., Croen, L., Water, J. V. D., & Ashwood, P. (2008) · American Journal of Biochemistry and Biotechnology · doi:10.3844/ajbbsp.2008.114.120 · Cited by 51
Interleukin-17 as a key player in neuroimmunometabolism
Douglas, A., Stevens, B., & Lynch, L. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00846-3 · Cited by 49
TGF-beta: a master switch in tumor immunity
Gigante, M., Gesualdo, L., & Ranieri, E. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212802430378 · Cited by 45
“[110] Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B.”
BackgroundUpdate 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
Neutralization of Interleukin‐17 Attenuates Cholestatic Liver Fibrosis in Mice
Zhang, S., Huang, D., Weng, J., Huang, Y., Liu, S., Zhang, Q., Li, N., Wen, M., Zhu, G., Lin, F., et al. (2016) · Scandinavian Journal of Immunology · doi:10.1111/sji.12395 · Cited by 36
Oleanolic acid regulates the Treg/Th17 imbalance in gastric cancer by targeting IL-6 with miR-98-5p
Xu, Q.-F., Peng, H.-P., Lu, X.-R., Hu, Y., Xu, Z.-H., & Xu, J.-K. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155656 · Cited by 36
Jeffery, H. C., Hunter, S., Humphreys, E. H., Bhogal, R., Wawman, R. E., Birtwistle, J., Atif, M., Bagnal, C. J., Rodriguez Blanco, G., Richardson, N., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1800455 · Cited by 35
Ferreira, R. C., Rainbow, D. B., Rubio García, A., Pekalski, M. L., Porter, L., Oliveira, J. J., Waldron-Lynch, F., Wicker, L. S., & Todd, J. A. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.03.002 · Cited by 19
Kim, B. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105254 · Cited by 8
Metadata
- Authors
- Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B.
- Affiliations
- National Institute for Medical Research (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Stockinger, Brigitta
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 24
- Issue
- 2
- Pages
- 179-189
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2112866067
- Cited by
- 3,605
- References
- 70
- Citations by year
- 2026: 41 · 2025: 54 · 2024: 71 · 2023: 91 · 2022: 110 · 2021: 149 · 2020: 113 · 2019: 114 · 2018: 122 · 2017: 158 · 2016: 138 · 2015: 172 · 2014: 182 · 2013: 219 · 2012: 246
- FWCI
- 126.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI30663, R01AI030663)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- IL-17-producing T cells, TGF-β1, Th17 cell differentiation, regulatory T cells, interleukin-6, TLR3, TLR4, TLR9, IL-1β, TNF-α, IL-23, GATA3, T-bet, Smad7, Th1/Th2 differentiation, naive CD4+ T cells, inflammatory cytokines
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Dendritic Cells, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, CD4-Positive T-Lymphocytes, Lymphocyte Subsets, Cytokines, Transforming Growth Factor beta, Receptors, Interleukin-1, Mice, Knockout, Th1 Cells, Th2 Cells, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Smad7 Protein, Transforming Growth Factor beta1
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