CXCL13 neutralization reduces the severity of collagen-induced arthritis.
CXCL13 neutralization reduces the severity of collagen-induced arthritis.
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DOI：
10.1002/art.20768
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发表时间：
2005-02
影响因子：
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通讯作者：
B. Zheng;Zeynep Ozen;Xuejun Zhang;S. De Silva;E. Marinova;Linjie Guo;Daniel L. Wansley;D. Huston;M. West;Shuhua Han
中科院分区：
文献类型：
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作者：
B. Zheng;Zeynep Ozen;Xuejun Zhang;S. De Silva;E. Marinova;Linjie Guo;Daniel L. Wansley;D. Huston;M. West;Shuhua Han
目的探讨CXCL 13在胶原诱导性关节炎（CIA）发生、发展中的作用，以及CXCL 13中和作用对CIA致关节炎反应的调节机制。方法用Ⅱ型胶原（CII）免疫小鼠，在加强免疫期间用抗CXCL 13抗体或对照抗体处理。监测小鼠关节炎的发展和严重程度。通过CII特异性T细胞的细胞因子产生和CII特异性抗体产生来评估CXCL 13中和对CII免疫应答的影响。通过原位免疫组织学测定脾脏和滑膜组织中的卵泡反应。结果与注射磷酸盐缓冲盐水或对照抗体的小鼠相比，接受CXCL 13中和抗体的小鼠关节炎严重程度显著降低。脾和滑膜组织中的卵泡反应均受到抗CXCL 13治疗的抑制。注射抗CXCL 13抗体并不显著影响体外抗原特异性回忆淋巴细胞增殖或1型细胞因子产生。抗CXCL 13处理不抑制对CII特异性的抗体应答。然而，在体外CII刺激后，抗CXCL 13治疗诱导显著更高水平的白细胞介素-10产生。结论CXCL 13的中和作用可抑制CIA的发生发展，降低淋巴组织和非淋巴组织的滤泡反应。这些发现可能对自身免疫性关节炎的发病机制和治疗具有重要意义。
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. CONCLUSION 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.