Role of CCRL2 in the pathogenesis of mouse experimental arthritis
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1
Department of Molecular and Translational Medicine, Italy
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2
Istituto Clinico Humanitas IRCCS, Italy
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3
University of Milan, Dept of Veterinary Pathology, Hygiene and Public Health,, Italy
Rheumatoid Arthritis (RA) is an autoimmune-mediated disease characterized by chronic inflammation and leukocyte recruitment into the inflamed joints. Chemokines and chemokine receptor activation are known to represent a major component of the effector molecules involved in the onset of RA.
CCRL2 [Chemokine (CC motif) receptor-like 2], also known as L-CCR, is a seven transmembrane protein that shows a high homology degree with many members of the CC chemokine receptor family. CCRL2 possesses a non-canonical DRYLIVE motif in the second intracellular loop that makes it to resemble like a nonsignaling chemotactic receptor (e.g. D6, DARC, CCX-CKR). CCRL2 is expressed by LPS-stimulated murine macrophages, neutrophils, mast cells, dendritic cells, glial cells, astrocytes and microglia and is up-regulated in human RA synovial neutrophils.
In order to elucidate the role of CCRL2 in RA, CCRL2 KO mice were tested in the model of collagen-induced arthritis. Only few CCRL2 KO mice displayed the pathological signs characteristic of arthritis with reduced leukocyte infiltration, synovial hyperplasia and joint erosions and with a significant reduction in visual scoring and paw thickness. Moreover, CCRL2 KO mice showed a marked delay (about ten days) in the onset of the disease and histological features reminiscent of recent joint damage. Conversely, the level of specific anti-collagen II IgG in the serum was similar in CCRL2 KO and control mice. The mechanisms underling the protection of CCRL2 mice in RA models are currently under investigation and will help to define whether CCRL2 may represent a new therapeutic target for RA.
Acknowledgements
IMI JU-BeTheCure,contract 115142-2
Keywords:
CCRL2,
atypical chemokine receptors,
Rheumatoid arthritis,
leukocyte trafficking,
Neutrophils
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
DEL PRETE
A,
Gonzalvo-Feo
S,
Wang
L,
Mazzon
C,
Scanziani
E,
Vecchi
A and
Sozzani
S
(2013). Role of CCRL2 in the pathogenesis of mouse experimental arthritis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00722
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Received:
17 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. ANNALISA DEL PRETE, Department of Molecular and Translational Medicine, Brescia, Italy, annalisa.delprete@unibs.it