Novel immunosuppressive properties of interleukin-6 in dendritic cells: inhibition of NF-kappaB binding activity and CCR7 expression

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Subramanya HegdeSigrun Smola-Hess

Abstract

Interleukin-6 (IL-6) is produced during bacterial and viral infections and by various malignant tumors. Here, we describe novel immunosuppressive properties of IL-6 in dendritic cells (DC). In the presence of GM-CSF, IL-4, and a maturation stimulus, IL-6 skewed monocyte differentiation into phenotypically mature but functionally impaired DC. In DC matured with the toll-like receptor (TLR)4 stimulus lipopolysaccharide (LPS) or other pro-inflammatory stimuli, IL-6 inhibited CCR7 chemokine receptor up-regulation. As demonstrated for LPS-stimulated DC, IL-6 impaired chemotaxis to CCR7-activating chemokines required for recruiting DC to lymphoid tissues in vivo. Moreover, IL-6 inhibited production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma inducible protein-10 (IP-10) in DC, and DC-driven allogeneic T cell proliferation in mixed lymphocyte reactions. CCR7 expression was blocked at the transcriptional level. IL-6 led to inhibition of nuclear factor-kappaB (NF-kappaB) binding activity, regulating CCR7 transcription. Neutralization experiments revealed that autocrine IL-10 partially contributed to CCR7 suppression in IL-6-treated DC. Thus IL-6, a cytokine once labeled as "pro-inflammatory" can mediate immunosuppres...Continue Reading

References

Jan 1, 1991·Annual Review of Immunology·R M Steinman
Jul 1, 1994·The Journal of Experimental Medicine·N RomaniG Schuler
Jan 1, 1993·Advances in Immunology·S AkiraT Kishimoto
Jan 1, 1996·The Journal of Experimental Medicine·S Hess, H Engelmann
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·K NatarajanB B Aggarwal
May 1, 1997·Molecular and Cellular Biology·A J WhitmarshR J Davis
Sep 18, 1997·Immunology Today·H TilgJ W Mier
Mar 20, 1998·International Reviews of Immunology·T Hirano
Apr 1, 1998·Nature·J Banchereau, R M Steinman
Oct 1, 1998·European Journal of Immunology·F SallustoA Lanzavecchia
Nov 5, 1999·The Journal of Biological Chemistry·A J SchotteliusA S Baldwin
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A C La FlammeE J Pearce
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S HessH Pfister
Feb 13, 2001·Immunity·Sean DiehlM Rincón
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J F ArrighiC Hauser
Dec 18, 2001·Nature Immunology·Simona SaccaniGioacchino Natoli
Aug 21, 2002·The Journal of Experimental Medicine·F GeissmannJ Davoust
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia NiemandGerhard Müller-Newen
May 20, 2003·Nature Immunology·Roland LangPeter J Murray
May 20, 2003·Nature Immunology·Hideo YasukawaAkihiko Yoshimura
May 30, 2003·The Biochemical Journal·Peter C HeinrichFred Schaper

❮ Previous
Next ❯

Citations

Jun 3, 2006·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Kirsten SiepmannJohn V Forrester
Oct 10, 2006·Cancer Metastasis Reviews·Michael R ShurinRobert L Ferris
May 3, 2013·PLoS Neglected Tropical Diseases·Shikha MalhotraJohn H Connor
Aug 16, 2008·Stem Cells·Mark L WeissKevin R McIntosh
Mar 7, 2009·The Journal of General Virology·Marion AbtSibylle Schneider-Schaulies
Dec 13, 2006·Biochemical and Biophysical Research Communications·Chang-Qing XiaMichael J Clare-Salzler
Nov 13, 2007·International Immunopharmacology·Lars Erik BartelsJens Frederik Dahlerup
Nov 12, 2013·Scientific Reports·Tania KonryMartin Yarmush
Nov 23, 2017·Frontiers in Psychiatry·Milica Milovan BorovcaninMiodrag L Lukic
Mar 7, 2018·Inflammopharmacology·Mohamad Akbari, Vahideh Hassan-Zadeh
Jun 4, 2014·Infection and Immunity·Tanya M JelacicArthur M Friedlander
Apr 3, 2012·The Journal of Rheumatology·Christophe RichezThierry Schaeverbeke
Aug 10, 2007·British Journal of Haematology·Guy PrattPaul Moss
Oct 16, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·John G LunzAnthony J Demetris
Feb 28, 2008·The Journal of Trauma·Guillermo M AlbaicetaFrancisco Taboada
Jun 28, 2008·Journal of Korean Medical Science·Hak-Mo LeeJeong Ryul Lee
Jun 6, 2007·European Journal of Immunology·Richard AppsAshley Moffett
Jul 20, 2010·Immunotherapy·David S RitchiePaul Neeson
Oct 19, 2013·International Journal of Cancer. Journal International Du Cancer·Jennifer Pahne-ZeppenfeldSigrun Smola
Dec 7, 2013·European Journal of Immunology·Natalia ZiętaraSiegfried Weiss
Aug 26, 2014·Frontiers in Microbiology·John Sinclair, Matthew Reeves
Sep 29, 2019·Cancer Immunology, Immunotherapy : CII·Marlene Fyrstenberg LaursenRalf Agger

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.