CXCL13 neutralization reduces the severity of collagen-induced arthritis.
OBJECTIVE
To investigate the role of CXCL13 in the development and pathogenesis of collagen-induced arthritis (CIA), and to determine the mechanisms involved in the modulation of arthritogenic response by CXCL13 neutralization.


METHODS
Mice were immunized with type II collagen (CII) and treated with anti-CXCL13 or control antibodies during boosting. Mice were monitored for the development and severity of arthritis. The effects of CXCL13 neutralization on immune response to CII were evaluated by cytokine production by CII-specific T cells and CII-specific antibody production. Follicular response in the spleen and in synovial tissue was determined by in situ immunohistology.


RESULTS
Mice receiving neutralizing antibodies to CXCL13 developed significantly less severe arthritis compared with mice injected with phosphate buffered saline or control antibodies. Follicular response both in the spleen and in synovial tissue was inhibited by anti-CXCL13 treatment. Injection with anti-CXCL13 antibodies did not significantly affect antigen-specific recall lymphocyte proliferation or type 1 cytokine production in vitro. Antibody response specific to CII was not inhibited by anti-CXCL13 treatment. However, anti-CXCL13 treatment induced significantly higher levels of interleukin-10 production after in vitro CII stimulation.


CONCLUSIONS
Neutralization of CXCL13 inhibits the development of CIA and reduces follicular response in both lymphoid and nonlymphoid tissues. These findings may have important implications regarding the pathogenesis and treatment of autoimmune arthritis.
Zheng
Biao
B
Baylor College of Medicine, Houston, Texas 77030, USA. bzheng@bcm.tmc.edu <bzheng@bcm.tmc.edu>
Ozen
Zeynep
Z
Zhang
Xuejun
X
De Silva
Swanthri
S
Marinova
Ekaterina
E
Guo
Linjie
L
Wansley
Daniel
D
Huston
David P
DP
West
Michael R
MR
Han
Shuhua
S
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000276:immunology*; D024043:Collagen Type II; D016207:Cytokines / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D013154:Spleen / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D024043:Collagen Type II; C486386:Cxcl13 protein, mouse; D016207:Cytokines; D016753:Interleukin-10