title: Up-regulation of Th17 cells may underlie inhibition of Treg development caused by immunization with activated syngeneic T cells.
abstract: BACKGROUND
  Our previous work showed that mice immunized with attenuated activated syngeneic T cells (aTCV) led to damping Treg function which resulted in enhancing anti-tumor immunity. It is well known that DC plays a very important role in controlling Th cell differentiation; whether DC involves Treg attenuation in immunized mice remained unknown. In this study, we provided evidence that increased mature DC (mDC) after immunization with aTCV skewed Th17 differentiation, which resulted in inhibition of Treg differentiation through IL-6 signaling pathway.
  
  
  RESULTS
  In the present study, we found that the frequency of mDCs increased dramatically in the immunized mice accompanied by lower Treg cells compared to the controls. Moreover, both DCs and serum derived from the immunized mice suppressed Treg differentiation in vitro, respectively. mDCs generated from bone marrow precursor cells in vitro strongly inhibited Treg development and simultaneously drove Th17 differentiation with elevated IL-6 production. However, PD-L1, a potent Treg inducer did not show effect on Treg down-regulation. Assay with transwell systems showed that cell-cell contact was necessary for IL-6 production to a threshold to activate Th17 transcriptional factor RORγt and to inhibit Treg counterpart Foxp3.
  
  
  CONCLUSIONS
  Our results implicate up-regulated Th17 development might be one of mechanisms of enhancing anti-tumor immunity induced by immunization with aTCV, which provide a novel insight in numerous mechanisms responsible for anti-tumor immunity.
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jinpiao
authors.initials: J
authors.lastname: Lin
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Rongfen
authors.initials: R
authors.lastname: Huo
authors.forename: Baihua
authors.initials: B
authors.lastname: Shen
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D019496:Cancer Vaccines / Q000494:pharmacology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells; D051858:Forkhead Transcription Factors; D007114:Immunization / Q000379:methods*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3
references.citation: Blood. 2007 Nov 1;110(9):3192-201
references.pmid: 17616639
references.citation: Immunotherapy. 2010 Jan;2(1):21-4
references.pmid: 20635888
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: Int Immunopharmacol. 2010 Sep;10(9):1055-61
references.pmid: 20601187
references.citation: Nat Rev Immunol. 2010 Apr;10(4):248-56
references.pmid: 20336152
references.citation: Immunity. 2009 May;30(5):646-55
references.pmid: 19464987
references.citation: Int Immunopharmacol. 2009 May;9(5):593-5
references.pmid: 19539563
references.citation: Immunity. 2009 Nov 20;31(5):787-98
references.pmid: 19879162
references.citation: Science. 2001 Oct 26;294(5543):870-5
references.pmid: 11679675
references.citation: J Clin Invest. 2009 Mar;119(3):551-64
references.pmid: 19229109
references.citation: Nature. 2006 May 11;441(7090):235-8
references.pmid: 16648838
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: J Immunol. 2005 May 15;174(10):5950-8
references.pmid: 15879087
references.citation: Nature. 2006 Jul 27;442(7101):461-5
references.pmid: 16688182
references.citation: Nat Rev Immunol. 2010 Mar;10(3):170-81
references.pmid: 20154735
references.citation: J Immunol. 2007 Jun 1;178(11):6730-3
references.pmid: 17513719
references.citation: J Exp Med. 2003 Jun 16;197(12):1689-99
references.pmid: 12810687
references.citation: Nat Rev Immunol. 2007 Jul;7(7):543-55
references.pmid: 17589544
references.citation: Science. 2003 Feb 14;299(5609):1033-6
references.pmid: 12532024
references.citation: J Exp Med. 2005 Jan 17;201(2):233-40
references.pmid: 15657292
references.citation: Biochem Biophys Res Commun. 2008 Sep 26;374(3):533-7
references.pmid: 18655770
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15505-10
references.pmid: 18832156
references.citation: Am J Pathol. 2007 Oct;171(4):1249-57
references.pmid: 17823289
references.citation: J Exp Med. 2005 May 16;201(10):1591-602
references.pmid: 15883172
references.citation: Curr Opin Immunol. 2007 Jun;19(3):309-14
references.pmid: 17433872
references.citation: J Immunol. 2009 Oct 15;183(8):4895-903
references.pmid: 19801514
references.citation: Cell Res. 2007 Jul;17(7):627-37
references.pmid: 17563757
references.citation: Cancer Res. 1999 Jul 1;59(13):3128-33
references.pmid: 10397255
references.citation: Immunity. 2009 May;30(5):616-25
references.pmid: 19464984
references.citation: Immunity. 2009 May;30(5):636-45
references.pmid: 19464986
references.citation: Science. 2001 Jul 13;293(5528):253-6
references.pmid: 11452116
references.citation: Oncol Rep. 2009 Aug;22(2):337-43
references.pmid: 19578774
references.citation: J Exp Med. 2009 Dec 21;206(13):3015-29
references.pmid: 20008522
references.citation: Cell Res. 2006 Aug;16(8):702-12
references.pmid: 16826163
references.citation: Blood. 2002 Mar 15;99(6):2114-21
references.pmid: 11877287
references.citation: J Immunol. 2006 May 15;176(10):6202-10
references.pmid: 16670330
references.citation: Science. 1998 Jan 16;279(5349):381-4
references.pmid: 9430588
references.citation: J Leukoc Biol. 2001 May;69(5):785-93
references.pmid: 11358988
references.citation: J Exp Med. 2004 Sep 20;200(6):771-82
references.pmid: 15381730
references.citation: Int Immunol. 2004 Dec;16(12):1769-80
references.pmid: 15520045