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    Monocytes/macrophages express CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation

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    Authors
    Schmutz, Caroline
    Cartwright, Alison
    Williams, Helen
    Haworth, Oliver
    Williams, John H. H.
    Filer, Andrew
    Salmon, Mike
    Buckley, Christopher D.
    Middleton, Jim F.
    Affiliation
    Keele University/University of Birmingham ; Keele University ; University of Chester ; University of Birmingham ; University of Chester ; University of Birmingham ; University of Birmingham ; University of Birmingham ; Keele University/University of Bristol
    Publication Date
    2010-08-05
    
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    Abstract
    Abstract Introduction 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.
    Citation
    Arthritis Research & Therapy, 2010, 12(4), R161
    Publisher
    BioMed Central
    Journal
    Arthritis Research & Therapy
    DOI
    10.1186/ar3120
    Additional Links
    http://arthritis-research.com
    Type
    Article
    Language
    en
    Description
    Available Gold OA
    ISSN
    1478-6354
    ae974a485f413a2113503eed53cd6c53
    10.1186/ar3120
    Scopus Count
    Collections
    Biological Sciences
    Biological Sciences
    Gold OA

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