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Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells

Heink, Sylvia, Yogev, Nir, Garbers, Christoph, Herwerth, Marina, Aly, Lilian, Gasperi, Christiane, Husterer, Veronika, Croxford, Andrew L, Möller-Hackbarth, Katja, Bartsch, Harald S, Sotlar, Karl, Krebs, Stefan, Regen, Tommy, Blum, Helmut, Hemmer, Bernhard, Misgeld, Thomas, Wunderlich, Thomas F, Hidalgo, Juan, Oukka, Mohamed, Rose-John, Stefan, Schmidt-Supprian, Marc, Waisman, Ari, Korn, Thomas·2017·Nature Immunology
DOI 10.1038/ni.3632PMC PMC5164931
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  4. Serada, S. et al. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 105, 9041–9046 (2008). · DOI
  5. Lee, Y. et al. Induction and molecular signature of pathogenic TH17 cells. Nat. Immunol. 13, 991–999 (2012). · DOI · Paper page
  6. Gaublomme, J.T. et al. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell 163, 1400–1412 (2015). · DOI · Paper page
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  12. Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448, 484–487 (2007). · DOI
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  14. Baran, P., Nitz, R., Grötzinger, J., Scheller, J. & Garbers, C. Minimal interleukin 6 (IL-6) receptor stalk composition for IL-6 receptor shedding and IL-6 classic signaling. J. Biol. Chem. 288, 14756–14768 (2013). · DOI
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  16. Fischer, M. et al. I. A bioactive designer cytokine for human hematopoietic progenitor cell expansion. Nat. Biotechnol. 15, 142–145 (1997). · DOI
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  18. Linker, R.A. et al. IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier. J. Neuroimmunol. 205, 64–72 (2008). · DOI
  19. Suto, A., Wurster, A.L., Reiner, S.L. & Grusby, M.J. IL-21 inhibits IFN-γ production in developing Th1 cells through the repression of Eomesodermin expression. J. Immunol. 177, 3721–3727 (2006). · DOI
  20. Yagi, R. et al. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-γ. Immunity 32, 507–517 (2010). · DOI
  21. Awasthi, A. et al. Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J. Immunol. 182, 5904–5908 (2009). · DOI
  22. Chu, C.Q., Wittmer, S. & Dalton, D.K. Failure to suppress the expansion of the activated CD4 T cell population in interferon γ-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J. Exp. Med. 192, 123–128 (2000). · DOI
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  25. Wuest, S.C. et al. A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat. Med. 17, 604–609 (2011). · DOI
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  28. Croxford, A.L., Mair, F. & Becher, B. IL-23: one cytokine in control of autoimmunity. Eur. J. Immunol. 42, 2263–2273 (2012). · DOI
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  32. Quintana, A. et al. Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav. Immun. 27, 162–173 (2013). · DOI
  33. Korn, T. et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13, 423–431 (2007). · DOI
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  35. Rabe, B. et al. Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 111, 1021–1028 (2008). · DOI
  36. Korn, T. et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 105, 18460–18465 (2008). · DOI
  37. Brakenhoff, J.P., Hart, M., De Groot, E.R., Di Padova, F. & Aarden, L.A. Structure-function analysis of human IL-6. Epitope mapping of neutralizing monoclonal antibodies with amino- and carboxyl-terminal deletion mutants. J. Immunol. 145, 561–568 (1990). · DOI

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Metadata

Authors
Heink, S., Yogev, N., Garbers, C., Herwerth, M., Aly, L., Gasperi, C., Husterer, V., Croxford, A. L., Möller-Hackbarth, K., Bartsch, H. S., Sotlar, K., Krebs, S., Regen, T., Blum, H., Hemmer, B., Misgeld, T., Wunderlich, T. F., Hidalgo, J., Oukka, M., Rose-John, S., Schmidt-Supprian, M., Waisman, A., & Korn, T.
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2016-11-28
Volume
18
Issue
1
Pages
74-85
ISSN
  • 1529-2908
  • 1529-2916
DOI
10.1038/ni.3632
PMC
PMC5164931
Cited by
386
References
10
Language
en
Update notices
erratum (2017-04-01)
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