title: Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression.
abstract: BACKGROUND
  This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls.
  
  
  METHODS
  MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences.
  
  
  RESULTS
  The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P <0.01 and fold-change <0.66 or >1.5). Four selected genes were validated by q
  ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2.
  
  
  CONCLUSIONS
  This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses.
authors.forename: Alice
authors.initials: A
authors.lastname: Talpin
authors.forename: Félicie
authors.initials: F
authors.lastname: Costantino
authors.forename: Nelly
authors.initials: N
authors.lastname: Bonilla
authors.forename: Ariane
authors.initials: A
authors.lastname: Leboime
authors.forename: Franck
authors.initials: F
authors.lastname: Letourneur
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacques
authors.forename: Florent
authors.initials: F
authors.lastname: Dumont
authors.forename: Sonia
authors.initials: S
authors.lastname: Amraoui
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Dutertre
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Garchon
authors.forename: Maxime
authors.initials: M
authors.lastname: Breban
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D025242:Spondylarthropathies / Q000235:genetics* / Q000276:immunology*; D059467:Transcriptome
chemical_list: D015796:HLA-B27 Antigen