Abstract
Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.
References
Sep 1, 1993·The Journal of Experimental Medicine·A D'AndreaG Trinchieri
Feb 1, 1997·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·D M TurnerI V Hutchinson
Jul 1, 1997·European Journal of Immunology·J C GuéryL Adorini
May 8, 1998·Scandinavian Journal of Rheumatology·A H HajeerW E Ollier
Jul 9, 1999·The Journal of Infectious Diseases·M HelminenM Hurme
Jul 23, 1999·Annals of the New York Academy of Sciences·L A PerottiA Angeli
Jul 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C J Edwards-SmithE E Powell
Nov 9, 2000·European Journal of Immunology·B LienenlükeM Hecker
Feb 15, 2001·Nature Genetics·G MorahanP G Colman
Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S CorintiG Girolomoni
Oct 17, 2001·The Journal of Experimental Medicine·R GrumontS Gerondakis
Sep 11, 2002·Journal of the Neurological Sciences·Kjell-Morten MyhrChristian A Vedeler
Sep 21, 2002·Lancet·Grant MorahanPatrick G Holt
Nov 9, 2002·Genes and Immunity·E ReussT Höhler
Nov 9, 2002·Genes and Immunity·G MorahanN M Anstey
Nov 9, 2002·Genes and Immunity·D SeegersG Bouma
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Saho MaruyamaYoshihiro Asano
May 7, 2003·The Journal of Experimental Medicine·Julie M CurtsingerMatthew F Mescher
Aug 7, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diego LaderachAnne Galy
Oct 22, 2003·The Journal of Experimental Medicine·Jianguo LiuXiaojing Ma
Jun 4, 2004·Genes and Immunity·J Müller-BerghausD Schadendorf
Oct 15, 2005·Journal of Immunotherapy·Judy C PengLars K Nielsen
Citations
Apr 14, 2010·Immunogenetics·Chintana PhawongSrisin Khusmith
Jul 27, 2010·Rheumatology International·Lyuba D MitevaSpaska A Stanilova
Jun 15, 2010·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·J WangH Shen
Dec 30, 2006·Biochemical and Biophysical Research Communications·Hao XuWenxi Wu
Aug 30, 2008·The Journal of Experimental Medicine·Stefan F MartinMarina A Freudenberg
Jan 15, 2008·Carcinogenesis·L M G MoonsP D Siersema
Apr 17, 2008·Human Molecular Genetics·Sandrine MarquetAlain J Dessein
Aug 9, 2011·BMC Genetics·John M Ong'echaDouglas J Perkins
Dec 17, 2009·Malaria Journal·Izumi NakaJun Ohashi
May 2, 2008·Genes and Immunity·M BarbierP Rihet
Dec 4, 2009·Genes and Immunity·G MorahanUNKNOWN Type I Diabetes Genetics Consortium
May 6, 2009·Experimental Lung Research·Birgit AhrensEckard Hamelmann
Mar 17, 2016·Mediators of Inflammation·Tammy OthWilfred T V Germeraad
Aug 16, 2008·Human Immunology·Lyuba Miteva, Spaska Stanilova
May 31, 2008·Journal of Autoimmunity·Grant MorahanRob Williams
Apr 30, 2015·PloS One·Otso ArponenPirjo Mustonen
Apr 10, 2016·Scandinavian Journal of Immunology·A Paradowska-GoryckaP P Jagodzinski
Oct 30, 2018·Small·Chenxia GuanChad A Mirkin
Sep 18, 2009·Clinical and Experimental Immunology·C BisseyeJ Ismaili
Mar 18, 2008·Clinical and Experimental Immunology·G K ChinE R Kaminski
Jul 29, 2010·British Journal of Cancer·X S Liu
May 15, 2008·International Journal of Cancer. Journal International Du Cancer·Andrew Mark JacksonPoulam M Patel
Jul 20, 2018·Scientific Reports·Yong SongGuicheng Brad Zhang
Apr 8, 2020·Frontiers in Public Health·Hongli GuanXiaohong Peng
Jan 12, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luciano CastielloDavid F Stroncek
Jan 6, 2021·Analytical Chemistry·Suttipong SuttapitugsakulRonghu Wu
Jan 31, 2015·Chemical Research in Toxicology·Adam V WisnewskiChristopher M Colangelo