Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Open accessAbstract
CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity. Although crucial for T(H)17 cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been proposed to be the factors responsible for initiating specification. Here we show that T(H)17 differentiation can occur in the absence of TGF-β signalling. Neither IL-6 nor IL-23 alone efficiently generated T(H)17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naive precursors, independently of TGF-β. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed RORγt (encoded by Rorc) and T-bet. T-bet(+)RORγt(+) T(H)17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred T(H)17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications.
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Produced IL-6 further induces Th17 cell differentiation through STAT3 in the presence of TGFβ, IL-1β and IL-23, which are rich in inflammatory lesions and tumor microenvironments.
“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 [171]
The paper’s main text (indexed under Abstract; page unavailable) says IL-6 acts through STAT3 and supports Th17 differentiation with TGF-β, or with IL-1β and IL-23 independently of TGF-β. It does not establish that all four cytokines act together as the sentence implies: it reports that TGF-β inhibits IL-23 receptor expression. It says TGF-β is present at sites of inflammation, but does not establish that all four cytokines are abundant there or in tumor microenvironments. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAcquisition of the pathogenic phenotype occurs after expression of IL-23R by TH17 cells.
“the acquisition of the pathogenic phenotype occurs after expression of the IL-23 receptor (IL-23R) by TH17 cells (Ghoreschi et al., 2010; Langrish et al., 2005)”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Ghoreschi et al., 2010
The passages under the Abstract heading (page unavailable) report that IL-6 and IL-1β induce Il23r expression and that Th17 cells generated with IL-23 have greater pathogenic potential in the EAE model. They do not establish the claimed sequence in which already-differentiated Th17 cells acquire a pathogenic phenotype after expressing IL-23R. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIL-23R expression is induced after stimulation by IL-21.
“which is induced after stimulation by IL-21.”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Ghoreschi et al., 2010
The passage on IL-23R induction (section labeled Abstract; page unavailable) reports induction of Il23r mRNA by IL-6 and IL-1β, with further enhancement by IL-23. Searches for IL-21 induction and for “IL-21 Il23r” found no passage showing that IL-21 stimulation induces IL-23R expression. The reported effects of other cytokines do not rule it out. (LLM, conf=0.72)
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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 · see citing works
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 · see citing works
Self-citationVeldhoen, 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 · see citing works
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 · see citing works
Self-citationAcosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857 · see citing works
IL-17 family cytokines and the expanding diversity of effector T cell lineages
Weaver, C. T., Hatton, R. D., Mangan, P. R., & Harrington, L. E. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141557 · Cited by 1,842 · see citing works
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 · see citing works
Late 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 · see citing works
Preferential recruitment of interferon‐γ–expressing T <sub>H</sub> 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 · see citing works
Flagged first, then by citations
Research works printed but not linked: 21
- [1]Miossec P Korn T Kuchroo VK Interleukin-17 and type 17 helper T cells N Engl J Med 361 888 898 2009 19710487
- [3]Stockinger B Veldhoen M Differentiation and function of Th17 T cells Curr Opin Immunol 19 281 286 2007 17433650
- [6]McGeachy MJ The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo Nat Immunol 10 314 324 2009 19182808 PMC2945605
- [8]Mangan PR Transforming growth factor-beta induces development of the T(H)17 lineage Nature 441 231 234 2006 16648837
- [11]Veldhoen M Hocking RJ Flavell RA Stockinger B Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease Nat Immunol 7 1151 1156 2006 16998492
- [12]Liu Y A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells Nat Immunol 9 632 640 2008 18438410
- [14]Das J Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation J Exp Med 206 2407 2416 2009 19808254 PMC2768861
- [15]Bettelli E Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis J Exp Med 200 79 87 2004 15238607 PMC2213316
- [16]Lochner M In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgammat+ T cells J Exp Med 205 1381 1393 2008 18504307 PMC2413035
- [17]Yang Y T-bet is essential for encephalitogenicity of both Th1 and Th17 cells J Exp Med 206 1549 1564 2009 19546248 PMC2715092
- [18]Aggarwal S Ghilardi N Xie MH de Sauvage FJ Gurney AL Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 J Biol Chem 278 1910 1914 2003 12417590
- [19]Park H A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 Nat Immunol 6 1133 1141 2005 16200068 PMC1618871
- [20]Harrington LE Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages Nat Immunol 6 1123 1132 2005 16200070
- [21]McGeachy MJ TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology Nat Immunol 8 1390 1397 2007 17994024
- [22]Wilson NJ Development, cytokine profile and function of human interleukin 17-producing helper T cells Nat Immunol 8 950 957 2007 17676044
- [23]Chen Z Tato CM Muul L Laurence A O’Shea JJ Distinct regulation of interleukin-17 in human T helper lymphocytes Arthritis Rheum 56 2936 2946 2007 17763419 PMC2323677
- [25]Elyaman W IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells Proc Natl Acad Sci U S A 106 12885 12890 2009 19433802 PMC2722314
- [26]Nowak EC IL-9 as a mediator of Th17-driven inflammatory disease J Exp Med 206 1653 1660 2009 19596803 PMC2722185
- [27]Gutcher I Urich E Wolter K Prinz M Becher B Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation Nat Immunol 7 946 953 2008 16906165
- [28]Lord GM T-bet is required for optimal proinflammatory CD4+ T-cell trafficking Blood 106 3432 3439 2005 16014561 PMC1895048
- [29]Koch MA The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation Nat Immunol 10 595 602 2009 19412181 PMC2712126
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Codarri, L., Gyülvészi, G., Tosevski, V., Hesske, L., Fontana, A., Magnenat, L., Suter, T., & Becher, B. (2011) · Nature Immunology · doi:10.1038/ni.2027 · Cited by 1,191 · see citing works
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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 · see citing works
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Komatsu, N., Okamoto, K., Sawa, S., Nakashima, T., Oh-hora, M., Kodama, T., Tanaka, S., Bluestone, J. A., & Takayanagi, H. (2014) · Nature Medicine · doi:10.1038/nm.3432 · Cited by 1,153 · see citing works
El-Behi, M., Ciric, B., Dai, H., Yan, Y., Cullimore, M., Safavi, F., Zhang, G.-X., Dittel, B. N., & Rostami, A. (2011) · Nature Immunology · doi:10.1038/ni.2031 · Cited by 1,071 · see citing works
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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 · see citing works
Microbiota: a key orchestrator of cancer therapy
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Single-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 · see citing works
Yang, X.-P., Ghoreschi, K., Steward-Tharp, S. M., Rodriguez-Canales, J., Zhu, J., Grainger, J. R., Hirahara, K., Sun, H.-W., Wei, L., Vahedi, G., et al. (2011) · Nature Immunology · doi:10.1038/ni.1995 · Cited by 583 · see citing works
Self-citationUshach, I., & Zlotnik, A. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0316-144r · Cited by 551 · see citing works
Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S., Hofmann, J., Raifer, H., Vachharajani, N., Carrascosa, L. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08711-2 · Cited by 508 · see citing works
The Role of IL-17 and related cytokines in inflammatory autoimmune diseases
Kuwabara, T., Ishikawa, F., Kondo, M., & Kakiuchi, T. (2017) · Mediators of Inflammation · doi:10.1155/2017/3908061 · Cited by 519 · see citing works
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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 · see citing works
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489 · see citing works
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Chalmin, F., Mignot, G., Bruchard, M., Chevriaux, A., Végran, F., Hichami, A., Ladoire, S., Derangère, V., Vincent, J., Masson, D., et al. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.019 · Cited by 338 · see citing works
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Komuczki, J., Tuzlak, S., Friebel, E., Hartwig, T., Spath, S., Rosenstiel, P., Waisman, A., Opitz, L., Oukka, M., Schreiner, B., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.006 · Cited by 201 · see citing works
Fang, D., & Zhu, J. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170494 · Cited by 175 · see citing works
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Self-citationLarochelle, C., Cayrol, R., Kebir, H., Alvarez, J. I., Lécuyer, M.-A., Ifergan, I., Viel, É., Bourbonnière, L., Beauseigle, D., Terouz, S., et al. (2012) · Brain · doi:10.1093/brain/aws212 · Cited by 145 · see citing works
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Ronchi, F., Basso, C., Preite, S., Reboldi, A., Baumjohann, D., Perlini, L., Lanzavecchia, A., & Sallusto, F. (2016) · Nature Communications · doi:10.1038/ncomms11541 · Cited by 115 · see citing works
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Slyepchenko, A., Maes, M., Köhler, C. A., Anderson, G., Quevedo, J., Alves, G. S., Berk, M., Fernandes, B. S., & Carvalho, A. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.002 · Cited by 89 · see citing works
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Thakore, P. I., Schnell, A., Zhao, M., Huang, L., Hou, Y., Christian, E., Zaghouani, S., Wang, C., Singh, V., Ma, S., et al. (2022) · doi:10.1101/2022.02.26.482041 · Cited by 57 · see citing works
Kanamori, Y., Murakami, M., Sugiyama, M., Hashimoto, O., Matsui, T., & Funaba, M. (2019) · Vitamins and Hormones · doi:10.1016/bs.vh.2019.01.007 · Cited by 47 · see citing works
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 · see citing works
Li, Y., Ye, Z., Zhu, J., Fang, S., Meng, L., & Zhou, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.844335 · Cited by 45 · see citing works
Sciurba, J. C., Gieseck, R. L., Jiwrajka, N., White, S. D., Karmele, E. P., Redes, J., Vannella, K. M., Henderson, N. C., Wynn, T. A., & Hart, K. M. (2019) · The Journal of Pathology · doi:10.1002/path.5215 · Cited by 22 · see citing works
- Authors
- 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., Grainger, J. R., Chen, Q., Kanno, Y., Watford, W. T., Sun, H.-W., Eberl, G., Shevach, E. M., Belkaid, Y., Cua, D. J., Chen, W., & O’Shea, J. J.
- Affiliations
- National Institutes of Health (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Institut Pasteur (FR)
- Corresponding author
- Ghoreschi, Kamran
- O’Shea, John J.
- ORCID
- Venue
- Nature
- Published
- 2010-10
- Volume
- 467
- Issue
- 7318
- Pages
- 967-971
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3108066
- OpenAlex
- W2015347941
- Cited by
- 1,388
- References
- 9
- Citations by year
- 2026: 31 · 2025: 58 · 2024: 65 · 2023: 87 · 2022: 72 · 2021: 92 · 2020: 76 · 2019: 90 · 2018: 84 · 2017: 104 · 2016: 94 · 2015: 107 · 2014: 109 · 2013: 104 · 2012: 113
- FWCI
- 43.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AR999999)
- 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 › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- Th17 cells, IL-23, interleukin-6, IL-1β, IL-17, RORγt, T-bet, autoimmunity, RORC, Th17 cell differentiation
- MeSH terms
- Interleukin-22, Animals, Autoimmune Diseases, Cell Differentiation, Central Nervous System, Inflammation, Interleukins, Mice, Inbred C57BL, Mucous Membrane, Signal Transduction, Autoimmunity, Interleukin-6, Transforming Growth Factor beta, Interleukin-10, Interleukin-9, Receptors, Interleukin, Interleukin-17, Mice, Interleukin-1beta, Interleukin-23, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells
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