Decreased Th17 and antigen-specific humoral responses in CX3CR1-deficient mice in the collagen-induced arthritis model

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 64; no. 5; pp. 1379 - 1387
• Main Authors: Tarrant, Teresa K., Liu, Peng, Rampersad, Rishi R., Esserman, Denise, Rothlein, Lisa R., Timoshchenko, Roman G., McGinnis, Marcus W., Fitzhugh, David J., Patel, Dhavalkumar D., Fong, Alan M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-05-2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Arthritis; Biological and medical sciences; Collagen; Diseases of the osteoarticular system; Immune system; Inflammatory joint diseases; Medical sciences; Immunopathology; Diseases of the osteoarticular system; Rodentia; Rheumatology; Autoimmune disease; Inflammatory joint disease; Antigen; Vertebrata; Chronic; Mammalia; Mouse; Animal; Rheumatoid arthritis; Models; Humoral immunity
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.34320

Objective
CX3CR1 is a chemokine receptor that uniquely binds to its ligand fractalkine (CX3CL1) and has been shown to be important in inflammatory arthritis responses, largely due to its effects on cellular migration. This study was undertaken to test the hypothesis that genetic deficiency of CX3CR1 is protective in the chronic inflammatory arthritis model collagen‐induced arthritis (CIA). Because CX3CR1 is expressed on T cells and antigen‐presenting cells, we also examined adaptive immune functions in this model.
Methods
Autoantibody formation, clinical, histologic, T cell proliferative, and cytokine responses were evaluated in wild‐type and CX3CR1‐deficient DBA/1J mice after immunization with heterologous type II collagen (CII).
Results
CX3CR1−/− mice had an ∼30% reduction in arthritis severity compared to wild‐type mice, as determined by 2 independent measures, paw swelling (P < 0.01) and clinical disease score (P < 0.0001). Additionally, compared to wild‐type mice, CX3CR1−/− mice had an ∼50% decrease in anti‐CII autoantibody formation (P < 0.05), decreased Th17 intraarticular cytokine expression (P < 0.01 for interleukin‐17 [IL‐17] and P < 0.001 for IL‐23), and decreased total numbers of Th17 cells in inflamed joints (P < 0.05).
Conclusion
Our findings indicate that CX3CR1 deficiency is protective in inflammatory arthritis and may have effects that extend beyond migration that involve adaptive immune responses in autoimmune disease.