title: FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis in rheumatoid arthritis.
abstract: BACKGROUND
  The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients.
  
  
  METHODS
  The levels of Flt3L in (paired) serum and synovial fluid (SF) were quantified by enzyme-link immunosorbent assay (ELISA). Expression of Flt3L and CD135 in paired peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) was quantified by fluorescence-activated cell sorting (FACS). The expression of Flt3L, CD135 and TNF-Converting Enzyme (TACE) in synovial tissues (STs) and in vitro polarized macrophages and monocyte-derived DCs (Mo-DCs) was assessed by quantitative PCR (qPCR). CD135 ST expression was evaluated by immunohistochemistry and TACE ST expression was assessed by immunofluorescence. Flt3L serum levels were assessed in RA patients treated with oral prednisolone or adalimumab.
  
  
  RESULTS
  Flt3L levels in RA serum, SF and ST were significantly elevated compared to gout patients and healthy individuals (HI). RA SF monocytes, natural killer cells and DCs expressed high levels of Flt3L and CD135 compared to HI. RA ST CD68+ and CD163+ macrophages, CD55+ fibroblast-like synoviocytes (FLS), CD31+ endothelial cells or infiltrating monocytes and CD19+ B cells co-expressed TACE. IFN-γ-differentiated macrophages expressed higher levels of Flt3L compared to other polarized macrophages. Importantly, Flt3L serum levels were reduced by effective therapy.
  
  
  CONCLUSIONS
  The Flt3L/CD135 axis is active in RA patients and is responsive to both prednisolone and adalimumab treatment. Conceivably, this ligand receptor pair represents a novel therapeutic target.
authors: Maria I
authors: MI
authors: Ramos
authors: Samuel Garcia
authors: SG
authors: Perez
authors: Saida
authors: S
authors: Aarrass
authors: Boy
authors: B
authors: Helder
authors: Pleun
authors: P
authors: Broekstra
authors: Daan M
authors: DM
authors: Gerlag
authors: Kris A
authors: KA
authors: Reedquist
authors: Paul Peter
authors: PP
authors: Tak
authors: Maria C
authors: MC
authors: Lebre
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3