Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin
Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin
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DOI：
10.1016/s1074-7613(03)00326-1
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发表时间：
2003-12-01
期刊：
影响因子：
32.4
通讯作者：
Carding, SR
中科院分区：
文献类型：
--
作者：
Ashcroft, AJ;Cruickshank, SM;Carding, SR
自身免疫相关的骨疾病和肠道炎症与自身反应性CD 4 T细胞的失调和过度活化密切相关。这些T细胞如何被激活并介导疾病尚不清楚。在这里，我们表明，在白细胞介素2缺乏小鼠模型的自身免疫性自发性骨质减少和结肠炎是由增加生产的配体NF κ B受体激活剂（RANKL）。RANKL通过其受体NF κ B受体激活剂（RANK）发挥作用，增加骨转换并促进体内肠树突状细胞（DC）存活。用外源性重组骨保护素（Fc-OPG）调节RANKL-RANK相互作用可逆转骨骼异常，并通过减少结肠DC数量减少结肠炎。这项研究确定了骨骼疾病和肠道炎症之间的共同因果关系，并建立了DC在体内介导结肠炎症的重要性。
Autoimmune associated bone disease and intestinal inflammation are closely linked with deregulation and hyperactivation of autoreactive CD4 T cells. How these T cells are activated and mediate disease is not clear. Here we show that in the Interleukin 2-deficient mouse model of autoimmunity spontaneous osteopenia and colitis are caused by increased production of the ligand for receptor activator of NFkappaB (RANKL). RANKL acting via its receptor, receptor activator of NFkappaB (RANK), increases bone turnover and promotes intestinal dendritic cell (DC) survival in vivo. Modulation of RANKL-RANK interactions with exogenous recombinant osteoprotegerin (Fc-OPG) reverses skeletal abnormalities and reduces colitis by decreasing colonic DC numbers. This study identifies a common causal link between bone disease and intestinal inflammation and establishes the importance of DC in mediating colonic inflammation in vivo.