Journal Article
. 2010 Mar;5(2).
doi: 10.1371/journal.pone.0009404.

Gene expression profiles identify inflammatory signatures in dendritic cells

Anna Torri 1 Ottavio Beretta  Anna Ranghetti  Francesca Granucci  Paola Ricciardi-Castagnoli  Maria Foti  
  • PMID: 20195376
  •     62 References
  •     20 citations


Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting leukocytes important in activation of both innate and adaptive immunity. We studied the gene expression patterns of DCs incubated with reagents inducing their activation or inhibition. Total RNA was isolated from DCs and gene expression profiling was performed with oligonucleotide microarrays. Using a supervised learning algorithm based on Random Forest, we generated a molecular signature of inflammation from a training set of 77 samples. We then validated this molecular signature in a testing set of 38 samples. Supervised analysis identified a set of 44 genes that distinguished very accurately between inflammatory and non inflammatory samples. The diagnostic performance of the signature genes was assessed against an independent set of samples, by qRT-PCR. Our findings suggest that the gene expression signature of DCs can provide a molecular classification for use in the selection of anti-inflammatory or adjuvant molecules with specific effects on DC activity.

Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor.
I Alroy, T L Towers, L P Freedman.
Mol Cell Biol, 1995 Oct 01; 15(10). PMID: 7565732    Free PMC article.
Highly Cited.
A power law global error model for the identification of differentially expressed genes in microarray data.
Norman Pavelka, Mattia Pelizzola, +4 authors, Paola Ricciardi-Castagnoli.
BMC Bioinformatics, 2004 Dec 21; 5. PMID: 15606915    Free PMC article.
Gene expression profiling during differentiation of human monocytes to macrophages or dendritic cells.
Anne Lehtonen, Helena Ahlfors, +3 authors, Ilkka Julkunen.
J Leukoc Biol, 2007 Jun 28; 82(3). PMID: 17595377
Outcome signature genes in breast cancer: is there a unique set?
Liat Ein-Dor, Itai Kela, +2 authors, Eytan Domany.
Bioinformatics, 2004 Aug 17; 21(2). PMID: 15308542
Highly Cited.
Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays.
U Alon, N Barkai, +4 authors, A J Levine.
Proc Natl Acad Sci U S A, 1999 Jun 09; 96(12). PMID: 10359783    Free PMC article.
Highly Cited.
An integrated method for cancer classification and rule extraction from microarray data.
Liang-Tsung Huang.
J Biomed Sci, 2009 Mar 11; 16. PMID: 19272192    Free PMC article.
Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens.
Michael J Zilliox, Giovanni Parmigiani, Diane E Griffin.
Proc Natl Acad Sci U S A, 2006 Feb 24; 103(9). PMID: 16492729    Free PMC article.
A central role for tissue-resident dendritic cells in innate responses.
Maria Foti, Francesca Granucci, Paola Ricciardi-Castagnoli.
Trends Immunol, 2004 Nov 09; 25(12). PMID: 15530834
Calculating confidence intervals for prediction error in microarray classification using resampling.
Wenyu Jiang, Sudhir Varma, Richard Simon.
Stat Appl Genet Mol Biol, 2008 Mar 04; 7(1). PMID: 18312213
A molecular signature of metastasis in primary solid tumors.
Sridhar Ramaswamy, Ken N Ross, Eric S Lander, Todd R Golub.
Nat Genet, 2002 Dec 07; 33(1). PMID: 12469122
Highly Cited.
Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1.
Sonya M Abraham, Toby Lawrence, +5 authors, Andrew R Clark.
J Exp Med, 2006 Aug 02; 203(8). PMID: 16880258    Free PMC article.
Highly Cited.
Inducible IL-2 production by dendritic cells revealed by global gene expression analysis.
F Granucci, C Vizzardelli, +6 authors, P Ricciardi-Castagnoli.
Nat Immunol, 2001 Aug 30; 2(9). PMID: 11526406
Highly Cited.
Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.
Itai Yanai, Hila Benjamin, +9 authors, Orit Shmueli.
Bioinformatics, 2004 Sep 25; 21(5). PMID: 15388519
Highly Cited.
Using random forest for reliable classification and cost-sensitive learning for medical diagnosis.
Fan Yang, Hua-zhen Wang, +2 authors, Wei-wen Cai.
BMC Bioinformatics, 2009 Feb 28; 10 Suppl 1. PMID: 19208122    Free PMC article.
Endogenous ligands of Toll-like receptors.
Min-Fu Tsan, Baochong Gao.
J Leukoc Biol, 2004 Jun 05; 76(3). PMID: 15178705
Highly Cited. Review.
Gene expression profiling predicts clinical outcome of breast cancer.
Laura J van 't Veer, Hongyue Dai, +13 authors, Stephen H Friend.
Nature, 2002 Feb 02; 415(6871). PMID: 11823860
Highly Cited.
Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures.
C Winzler, P Rovere, +6 authors, P Ricciardi-Castagnoli.
J Exp Med, 1997 Jan 20; 185(2). PMID: 9016880    Free PMC article.
Highly Cited.
Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes.
Izidore S Lossos, Debra K Czerwinski, +4 authors, Ronald Levy.
N Engl J Med, 2004 Apr 30; 350(18). PMID: 15115829
Highly Cited.
Transcriptome profiling of primary murine monocytes, lung macrophages and lung dendritic cells reveals a distinct expression of genes involved in cell trafficking.
Zbigniew Zasłona, Jochen Wilhelm, +4 authors, Werner von Wulffen.
Respir Res, 2009 Jan 20; 10. PMID: 19149869    Free PMC article.
Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity.
Sandip Bhattacharyya, Pradip Sen, +3 authors, Roland Tisch.
Blood, 2004 Apr 29; 104(4). PMID: 15113757
Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays.
Weixue Zhong, Min Fei, Yibei Zhu, Xueguang Zhang.
Cell Mol Biol Lett, 2009 Jun 26; 14(4). PMID: 19554266    Free PMC article.
A type I IFN-dependent pathway induced by Schistosoma mansoni eggs in mouse myeloid dendritic cells generates an inflammatory signature.
François Trottein, Norman Pavelka, +9 authors, Paola Ricciardi-Castagnoli.
J Immunol, 2004 Feb 24; 172(5). PMID: 14978105
Identification of rab20 as a potential regulator of connexin 43 trafficking.
Jayasri Das Sarma, Benjamin E Kaplan, Dounia Willemsen, Michael Koval.
Cell Commun Adhes, 2008 Jul 24; 15(1). PMID: 18649179
Signatures of the immune response.
A L Shaffer, A Rosenwald, +4 authors, L M Staudt.
Immunity, 2001 Sep 25; 15(3). PMID: 11567628
Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance.
Stephanie Dillon, Sudhanshu Agrawal, +10 authors, Bali Pulendran.
J Clin Invest, 2006 Mar 18; 116(4). PMID: 16543948    Free PMC article.
Highly Cited.
Immunomodulation by 1,25-dihydroxyvitamin D3: therapeutic implications in hemodialysis and renal transplantation.
C Mathieu, M Jafari.
Clin Nephrol, 2006 Oct 27; 66(4). PMID: 17063995
A DNA microarray survey of gene expression in normal human tissues.
Radha Shyamsundar, Young H Kim, +7 authors, Jonathan R Pollack.
Genome Biol, 2005 Mar 19; 6(3). PMID: 15774023    Free PMC article.
Gene expression signatures in CD34+-progenitor-derived dendritic cells exposed to the chemical contact allergen nickel sulfate.
Elke Schoeters, Jean-Marie Nuijten, +6 authors, Geert R Verheyen.
Toxicol Appl Pharmacol, 2006 Jun 20; 216(1). PMID: 16780908
Gene expression microarrays: glimpses of the immunological genome.
Gordon Hyatt, Rachel Melamed, +15 authors, Christophe Benoist.
Nat Immunol, 2006 Jun 21; 7(7). PMID: 16785882
Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system.
John J Hutton, Anil G Jegga, +5 authors, Bruce J Aronow.
BMC Genomics, 2004 Oct 27; 5. PMID: 15504237    Free PMC article.
Elevated expression of TARC (CCL17) and MDC (CCL22) in models of cigarette smoke-induced pulmonary inflammation.
Mirko Ritter, Rolf Göggel, +4 authors, Peter Seither.
Biochem Biophys Res Commun, 2005 Jul 05; 334(1). PMID: 15993846
Dendritic cells and cytokines in human inflammatory and autoimmune diseases.
Patrick Blanco, A Karolina Palucka, Virginia Pascual, Jacques Banchereau.
Cytokine Growth Factor Rev, 2008 Feb 09; 19(1). PMID: 18258476    Free PMC article.
Highly Cited. Review.
Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.
Florence Allantaz, Damien Chaussabel, +12 authors, Virginia Pascual.
J Exp Med, 2007 Aug 29; 204(9). PMID: 17724127    Free PMC article.
IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1,25 dihydroxyvitamin D3.
D L Lacey, L E Grosso, +4 authors, D T Villareal.
J Clin Invest, 1993 Apr 01; 91(4). PMID: 8473513    Free PMC article.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Gene selection and classification of microarray data using random forest.
Ramón Díaz-Uriarte, Sara Alvarez de Andrés.
BMC Bioinformatics, 2006 Jan 10; 7. PMID: 16398926    Free PMC article.
Highly Cited.
Effects of dexamethazone on LPS-induced activationand migration of mouse dendritic cells revealed by a genome-wide transcriptional analysis.
Caterina Vizzardelli, Norman Pavelka, +8 authors, Paola Ricciardi-Castagnoli.
Eur J Immunol, 2006 May 19; 36(6). PMID: 16708398
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
A A Alizadeh, M B Eisen, +28 authors, L M Staudt.
Nature, 2000 Feb 17; 403(6769). PMID: 10676951
Highly Cited.
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.
Yixin Wang, Jan G M Klijn, +11 authors, John A Foekens.
Lancet, 2005 Feb 22; 365(9460). PMID: 15721472
Highly Cited.
Toll-like receptors in systemic autoimmune disease.
Ann Marshak-Rothstein.
Nat Rev Immunol, 2006 Oct 26; 6(11). PMID: 17063184    Free PMC article.
Highly Cited. Review.
Individuality and variation in gene expression patterns in human blood.
Adeline R Whitney, Maximilian Diehn, +4 authors, Patrick O Brown.
Proc Natl Acad Sci U S A, 2003 Feb 13; 100(4). PMID: 12578971    Free PMC article.
Highly Cited.
Regulation of IL-1 family cytokines IL-1alpha, IL-1 receptor antagonist, and IL-18 by 1,25-dihydroxyvitamin D3 in primary keratinocytes.
Juan Kong, Sergei A Grando, Yan Chun Li.
J Immunol, 2006 Mar 07; 176(6). PMID: 16517748
Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1).
J Z Zhang, K Maruyama, +2 authors, F Kaneko.
J Dermatol Sci, 1994 Feb 01; 7(1). PMID: 8193081
Innate immunity.
R Medzhitov, C Janeway.
N Engl J Med, 2000 Aug 03; 343(5). PMID: 10922424
Highly Cited. Review.
Breast cancer heterogeneity: evaluation of clonality in primary and metastatic lesions.
W F Symmans, J Liu, D M Knowles, G Inghirami.
Hum Pathol, 1995 Feb 01; 26(2). PMID: 7860051
Profiling dendritic cell maturation with dedicated microarrays.
Dorian McIlroy, Séverine Tanguy-Royer, +5 authors, Marc Grégoire.
J Leukoc Biol, 2005 Jun 18; 78(3). PMID: 15961579
Incubation of T cell or monocytic cell lines with 1,25-dihydroxyvitamin D3 before mitogen stimulation potentiates IL-2 and IL-1 beta mRNA levels.
J L Prehn, S C Jordan.
Transplant Proc, 1989 Feb 01; 21(1 Pt 1). PMID: 2784909
Dendritic cells and the control of immunity.
J Banchereau, R M Steinman.
Nature, 1998 Apr 01; 392(6673). PMID: 9521319
Highly Cited. Review.
Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous.
L Pirami, B Stockinger, +5 authors, P Ricciardi-Castagnoli.
Proc Natl Acad Sci U S A, 1991 Sep 01; 88(17). PMID: 1715569    Free PMC article.
Characterization of monocyte-derived dendritic cells maturated with IFN-alpha.
I M Svane, K Nikolajsen, +4 authors, A E Pedersen.
Scand J Immunol, 2006 Feb 28; 63(3). PMID: 16499575
A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana.
Toni Aebischer, Clare L Bennett, +9 authors, Paola Ricciardi-Castagnoli.
Eur J Immunol, 2005 Jan 20; 35(2). PMID: 15657947
Taking dendritic cells into medicine.
Ralph M Steinman, Jacques Banchereau.
Nature, 2007 Sep 28; 449(7161). PMID: 17898760
Highly Cited. Review.
IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells.
Thomas Luft, Petra Luetjens, +7 authors, Eugene Maraskovsky.
Int Immunol, 2002 Apr 06; 14(4). PMID: 11934873
Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts.
Evelyne van Etten, Chantal Mathieu.
J Steroid Biochem Mol Biol, 2005 Jul 28; 97(1-2). PMID: 16046118
Highly Cited. Review.
Toll-like receptors: critical proteins linking innate and acquired immunity.
S Akira, K Takeda, T Kaisho.
Nat Immunol, 2001 Jul 31; 2(8). PMID: 11477402
Highly Cited. Review.
A hybrid approach for biomarker discovery from microarray gene expression data for cancer classification.
Yanxiong Peng, Wenyuan Li, Ying Liu.
Cancer Inform, 2007 Jan 01; 2. PMID: 19458773    Free PMC article.
Dendritic cell interactions and cytokine production.
M Foti, F Granucci, P Ricciardi-Castagnoli.
Ernst Schering Res Found Workshop, 2005 Dec 07; (56). PMID: 16329646
Gene expression profiling of dendritic cells by microarray.
Maria Foti, Paola Ricciardi-Castagnoli, Francesca Granucci.
Methods Mol Biol, 2007 Sep 19; 380. PMID: 17876096
A shared gene-expression signature in innate-like lymphocytes.
Tetsuya Yamagata, Christophe Benoist, Diane Mathis.
Immunol Rev, 2006 Apr 21; 210. PMID: 16623764
Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
T R Golub, D K Slonim, +9 authors, E S Lander.
Science, 1999 Oct 16; 286(5439). PMID: 10521349
Highly Cited.
Gene expression profiling of dendritic cells by DNA microarrays.
Xin-Sheng Ju, Martin Zenke.
Immunobiology, 2004 Oct 16; 209(1-2). PMID: 15481149
Exploration, normalization, and summaries of high density oligonucleotide array probe level data.
Rafael A Irizarry, Bridget Hobbs, +4 authors, Terence P Speed.
Biostatistics, 2003 Aug 20; 4(2). PMID: 12925520
Highly Cited.
Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35.
Bertrand Evrard, Sophie Coudeyras, +4 authors, Christiane Forestier.
PLoS One, 2011 May 03; 6(4). PMID: 21533162    Free PMC article.
Gene expression profiling of dendritic cells reveals important mechanisms associated with predisposition to Staphylococcus infections.
Mehdi Toufeer, Cécile M D Bonnefont, +6 authors, Gilles Foucras.
PLoS One, 2011 Aug 23; 6(8). PMID: 21857913    Free PMC article.
Classification of dendritic cell phenotypes from gene expression data.
Giacomo Tuana, Viola Volpato, +3 authors, Maria Foti.
BMC Immunol, 2011 Aug 31; 12. PMID: 21875438    Free PMC article.
TLR agonists downregulate H2-O in CD8alpha- dendritic cells.
Gavin W Porter, Woelsung Yi, Lisa K Denzin.
J Immunol, 2011 Sep 16; 187(8). PMID: 21918198    Free PMC article.
Murine dendritic cells transcriptional modulation upon Paracoccidioides brasiliensis infection.
Aldo H Tavares, Lorena S Derengowski, +6 authors, Ildinete Silva-Pereira.
PLoS Negl Trop Dis, 2012 Jan 12; 6(1). PMID: 22235359    Free PMC article.
The use of classification trees for bioinformatics.
Xiang Chen, Minghui Wang, Heping Zhang.
Wiley Interdiscip Rev Data Min Knowl Discov, 2011 Jan 01; 1(1). PMID: 22523608    Free PMC article.
Neddylation plays an important role in the regulation of murine and human dendritic cell function.
Nathan Mathewson, Tomomi Toubai, +7 authors, Pavan Reddy.
Blood, 2013 Jul 19; 122(12). PMID: 23863900    Free PMC article.
A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.
David G Hancock, Elena Shklovskaya, +5 authors, Barbara Fazekas de St Groth.
PLoS One, 2014 Jun 21; 9(6). PMID: 24949855    Free PMC article.
Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics.
Julio Plaza-Diaz, Carolina Gomez-Llorente, Luis Fontana, Angel Gil.
World J Gastroenterol, 2014 Nov 18; 20(42). PMID: 25400447    Free PMC article.
Systematic Review.
Interferon-γ-inducible Rab20 regulates endosomal morphology and EGFR degradation in macrophages.
Gang Pei, Laura Schnettger, +3 authors, Maximiliano Gabriel Gutierrez.
Mol Biol Cell, 2015 Jul 15; 26(17). PMID: 26157167    Free PMC article.
Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205.
Luciana D'Apice, Valerio Costa, +3 authors, Piergiuseppe De Berardinis.
J Immunol Res, 2015 Sep 18; 2015. PMID: 26380324    Free PMC article.
Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses.
Geir Bredholt, Monica Mannelqvist, +9 authors, Lars A Akslen.
Oncotarget, 2015 Oct 21; 6(37). PMID: 26485755    Free PMC article.
IL-22 is rapidly induced by Pathogen Recognition Receptors Stimulation in Bone-Marrow-derived Dendritic Cells in the Absence of IL-23.
Silvia Fumagalli, Anna Torri, +3 authors, Maria Foti.
Sci Rep, 2016 Sep 23; 6. PMID: 27652524    Free PMC article.
ImpulseDE: detection of differentially expressed genes in time series data using impulse models.
Jil Sander, Joachim L Schultze, Nir Yosef.
Bioinformatics, 2016 Nov 01; 33(5). PMID: 27797772    Free PMC article.
Tolerogenic Transcriptional Signatures of Steady-State and Pathogen-Induced Dendritic Cells.
Emilia Vendelova, Diyaaeldin Ashour, +4 authors, Manfred B Lutz.
Front Immunol, 2018 Mar 16; 9. PMID: 29541071    Free PMC article.
Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis.
Faye A H Cooles, Amy E Anderson, +5 authors, John D Isaacs.
Front Immunol, 2018 Jun 06; 9. PMID: 29867920    Free PMC article.
Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer.
Charles C Guo, Tadeusz Majewski, +22 authors, Bogdan Czerniak.
Cell Rep, 2019 May 09; 27(6). PMID: 31067463    Free PMC article.
Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia.
Jonathon L Payne, Chunhua Song, +7 authors, Sinisa Dovat.
Int J Mol Sci, 2020 Mar 07; 21(5). PMID: 32138279    Free PMC article.
Assessment of Luminal and Basal Phenotypes in Bladder Cancer.
Charles C Guo, Jolanta Bondaruk, +18 authors, Bogdan Czerniak.
Sci Rep, 2020 Jun 18; 10(1). PMID: 32546765    Free PMC article.
Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways.
Mariolina Bruno, Intan M W Dewi, +12 authors, Frank L van de Veerdonk.
Comput Struct Biotechnol J, 2021 Jan 30; 19. PMID: 33510868    Free PMC article.