Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


CX3CR1 Deficient Mice Have Decreased Th17 and Antigen-Specific Humoral Responses in the Collagen Induced Arthritis (CIA) Model.

Tarrant2,  Teresa K., Liu3,  Peng, Rampersad3,  Rishi, Esserman3,  Denise, Rothlein3,  Lisa, McGinnis3,  Marcus W., Fitzhugh3,  David J.

Novartis Pharma AG, Basel, Switzerland
UNC School of Medicine, Chapel Hill, NC
UNC School of Medicine

Objective:

CX3CR1 is a chemokine receptor that uniquely binds to its ligand fracktalkine (FKN or CX3CL1) and has been shown to be important in inflammatory arthritis responses, largely due to effects on cellular migration. In this study, we tested the hypothesis that genetic deficiency of CX3CR1 would be protective in the chronic inflammatory arthritis model, collagen induced arthritis (CIA). Because CX3CR1 is expressed on T cells and antigen-presenting cells, we additionally examined adaptive immune functions in this model.

Methods:

Autoantibody formation, clinical, histologic, T cell proliferative, and cytokine responses were evaluated in DBA-1J mice deficient in (-/-) or wildtype (+/+) for CX3CR1 after immunization with heterologous type II collagen.

Results:

CX3CR1-/- mice had an approximately 30% reduction in arthritis by two independent measures of paw swelling (p<0.01) and clinical disease index(p<0.0001).

CX3CR1-/- mice had an approximate 50% decrease in anti-type II collagen antibody formation (p<0.05). Additionally, CX3CR1-/- mice had a unique 5-fold decrease in intra-articular levels of IL-17 (p<0.002), as measured by RT-PCR, despite a preserved capacity to induce Th17 de novo responses in vitro.

Proinflammatory MMP-13 and cytokines IL-6, IL-1b, and TNF-a were reduced in CX3CR1-/- mice, but were not statistically significant.

Conclusions:

Deficiency of CX3CR1 is protective in inflammatory arthritis and may have effects that extend beyond migration that involve adaptive immune responses.

To cite this abstract, please use the following information:
Tarrant, Teresa K., Liu, Peng, Rampersad, Rishi, Esserman, Denise, Rothlein, Lisa, McGinnis, Marcus W., et al; CX3CR1 Deficient Mice Have Decreased Th17 and Antigen-Specific Humoral Responses in the Collagen Induced Arthritis (CIA) Model. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :19
DOI: 10.1002/art.27789

Abstract Supplement

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