title: Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation.
abstract: BACKGROUND
  Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers.
  
  
  METHODS
  CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function.
  
  
  RESULTS
  CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia, CCR9 co-localised with cluster of differentiation 14+ (CD14+) and cluster of differentiation 68+ (CD68+) macrophages, and was more abundant in RA synovium. CCR9 mRNA was detected in the synovia of all RA patients and in some non-RA controls, and monocytes/macrophages from PB and SF of RA and healthy controls. CCL25 was detected in RA and non-RA synovia where it co-localised with CD14+ and CD68+ cells. Tumour necrosis factor alpha (TNFα) increased CCR9 expression on human acute monocytic leukemia cell line THP-1 monocytic cells. CCL25 induced a stronger monocyte differentiation in RA compared to healthy donors. CCL25 induced significant chemotaxis of PB monocytes but not consistently among individuals.
  
  
  CONCLUSIONS
  CCR9 expression by monocytes is increased in RA. CCL25 may be involved in the differentiation of monocytes to macrophages particularly in RA.
authors.affiliation: Leopold Muller Arthritis Research Centre, Keele University, Oswestry, Shropshire, SY10 7AG, UK. c.schmutz@bham.ac.uk
authors.forename: Caroline
authors.initials: C
authors.lastname: Schmutz
authors.forename: Alison
authors.initials: A
authors.lastname: Cartwright
authors.forename: Helen
authors.initials: H
authors.lastname: Williams
authors.forename: Oliver
authors.initials: O
authors.lastname: Haworth
authors.forename: John H H
authors.initials: JH
authors.lastname: Williams
authors.forename: Andrew
authors.initials: A
authors.lastname: Filer
authors.forename: Mike
authors.initials: M
authors.lastname: Salmon
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Jim
authors.initials: J
authors.lastname: Middleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D054388:Receptors, CCR / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D054388:Receptors, CCR; D014409:Tumor Necrosis Factor-alpha