Experimental arthritis in CC chemokine receptor 2-null mice closely mimics severe human rheumatoid arthritis.
Experimental arthritis in CC chemokine receptor 2-null mice closely mimics severe human rheumatoid arthritis.
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CC趋化因子受体2缺失小鼠的实验性关节炎与严重的人类类风湿性关节炎非常相似。
DOI：
10.1172/jci20126
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Ahuja,SeemaS
中科院分区：
文献类型：
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作者：
Quinones,MarlonP;Ahuja,SunilK;Jimenez,Fabio;Schaefer,Jason;Garavito,Edgar;Rao,Arun;Chenaux,George;Reddick,RobertL;Kuziel,WilliamA;Ahuja,SeemaS
The prevailing paradigm is that in human rheumatoid arthritis (RA), the accumulation of monocytes and T cells in the joint, mediated in part by such CC chemokine receptors (CCRs) as CCR2 and CCR5, respectively, plays a central role in disease pathogenesis. To further validate this paradigm, we conducted proof-of-principle studies and tested the hypothesis that gene inactivation ofCcr2orCcr5will ameliorate experimental RA. Contrary to our expectations, we found that in two well-established murine models of experimental RA, CCR2 expression in the hematopoietic cell compartment served as a negative regulator of autoantibody production as well as arthritic disease onset, severity, and resolution. In contrast, the RA phenotype inCcr5-null mice was similar to that of WT mice. Remarkably, the collagen-induced arthritis phenotype ofCcr2–/–mice mimicked closely that of severe human RA, including production of rheumatoid factor, enhanced T cell production, and monocyte/macrophage accumulation in the joints. Our findings demonstrate an essential protective role of CCR2 expression in RA, indicate the existence of alternative receptors responsible for monocyte/macrophage accumulation to inflamed joints, and emphasize the need to clarify carefully the complex effects of the chemokine system in RA before they can be considered as therapeutic targets.
