Open Access Research article

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

Caroline Schmutz12, Alison Cartwright1, Helen Williams3, Oliver Haworth2, John HH Williams3, Andrew Filer2, Mike Salmon2, Christopher D Buckley2 and Jim Middleton14*

Author Affiliations

1 Leopold Muller Arthritis Research Centre, Medical School, Keele University, RJAH Orthopaedic Hospital, Oswestry, Shropshire, SY10 7AG, UK

2 Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK

3 Chester Centre for Stress Research, University of Chester, Parkgate Road, Chester CH1 4BJ, UK

4 Dept of Oral and Dental Science, Faculty of Medicine and Dentistry, Lower Maudlin Street, University of Bristol, BS1 2LY, UK

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Arthritis Research & Therapy 2010, 12:R161  doi:10.1186/ar3120

Published: 25 August 2010

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 (TNF╬▒) 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.