Open Journal of Rheumatology and Autoimmune Diseases, 2012, 2, 77-84 http://dx.doi.org/10.4236/ojra.2012.24015 Published Online November 2012 (http://www.SciRP.org/journal/ojra) 77 Is Chemokine Receptor CCR9 Required for Synovitis in Rheumatoid Arthritis? Deficiency of CCR9 in a Murine Model of Antigen-Induced Arthritis Alison Cartwright 1 , Sophie King 2 , Jim Middleton 1,2 , Oksana Kehoe 1 1 Keele University at Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK; 2 Faculty of Medicine and Dentistry, School of Oral and Dental Sciences, University of Bristol, Bristol, UK. Email: Alison.Cartwright@rjah.nhs.uk Received July 27 th , 2012; revised September 10 th , 2012; accepted September 19 th , 2012 ABSTRACT Objectives: Monocytes/macrophages accumulate in the synovial membrane in rheumatoid arthritis and play a key role in disease pathogenesis, contributing to inflammation, cartilage destruction and bone erosion. Identification of mole- cules involved in monocyte/macrophage recruitment in inflammation is crucial for development of therapeutic interven- tions. Chemokine receptor CCR9 is up-regulated on these cells in peripheral blood and synovium of rheumatoid patients. This study investigated the course of antigen-induced arthritis in CCR9 deficient C57BL/6 mice in comparison to wild type animals to determine whether CCR9 is critical for disease severity and progression. Methods: Methylated bovine serum albumin was used for induction of uni-lateral arthritis by direct injection into the knee joints of preimmunized animals. Arthritis is confined to the injected joint allowing comparison with the normal opposing joint. Clinical severity of arthritis was assessed by measuring swelling in the arthritic joint in comparison to the normal joint. Histological analysis was performed to assess the extent of leukocyte infiltration and cartilage depletion. Results: Levels of swelling were not significantly different between wild type and CCR9 deficient mice. Similarly there was no significant differ- ence in histological severity of arthritis when comparing CCR9-deficient mice to wild type mice. Conclusions: CCR9 was not required for development of synovial inflammation and cartilage destruction in the antigen-induced model of arthritis in C57BL/6 mice in this study. This may reflect a true lack of a pathogenic role of CCR9 on mono- cyte/macrophage function in vivo or it may reflect differences in the current antigen-induced arthritis model when com- pared to human RA. Keywords: Chemokine Receptor CCR9; Rheumatoid Arthritis; Inflammation; Antigen-Induced Arthritis; Mouse Model; Monocytes/Macrophages 1. Introduction Rheumatoid Arthritis (RA) is a chronic inflammatory dis- ease characterized by the accumulation of leukocytes in the synovial membrane and fluid of affected joints. Che- mokine receptors on leukocytes mediate the persistent recruitment of these cells and identification of involved receptors offers potential for development of therapeutic interventions. Monocytes/macrophages play a key role in RA, contributing to inflammation, cartilage destruction and bone erosion. Monocytes migrate from the blood across the vascular endothelium into the synovium where they differentiate into macrophages. Activated macro- phages produce large quantities of pro-inflammatory cyto- kines and chemokines including interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNFα), IL-6, chemokine ligands CXCL8, CCL2 and CCL3, and also proteases such as matrix metalloproteinase MMP-9 and MMP-12 [1,2]. The degree of macrophage infiltration correlates to the radiological progression of joint destruction [3]. Chemokine receptor CCR9 is constitutively expressed on T lymphocytes in the small intestine, thymus, lymph node and spleen [4,5] with involvement in T cell recruit- ment to the small intestine and T cell development and migration within the thymus. CCR9 mediates migration of malignant cluster of dif- ferentiation 4 + (CD4 + ) T lymphocytes into various organs such as the lymph nodes, liver, spleen, lungs and intesti- nal tract in T-cell lineage acute lymphocytic leukaemia (T-ALL) [6]. CCR9 and its ligand CCL25 were found to be highly over-expressed on T-ALL CD4 + T cells when compared to normal CD4 + T cells. Human cutaneous melanoma cells are suggested to metastasize to the small intestine via action of CCR9 [7]. CCR9 also has roles in the metastatic spread of tumour cells in prostate cancer [8] Copyright © 2012 SciRes. OJRA