Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice
Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice
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DOI：
10.1111/j.1365-2567.2005.02290.x
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发表时间：
2006-03-01
期刊：
影响因子：
6.4
通讯作者：
Cantorna, MT
中科院分区：
文献类型：
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作者：
Froicu, M;Zhu, Y;Cantorna, MT
维生素D受体（VDR）是一种在免疫系统的许多不同细胞中表达的核受体。本研究旨在确定VDR缺乏对炎症性肠病模型（即白细胞介素-10（IL-10）敲除小鼠）免疫功能和胃肠道炎症的影响。产生IL-10敲除小鼠，其可以或不能对维生素D应答（双重IL-10/VDR敲除; DKO）。比较了淋巴细胞在初级和次级淋巴器官中的分布和功能，并确定其为肠道炎症严重程度的函数。DKO小鼠在3周龄时具有正常的胸腺发育和外周T细胞数量，但在检测到肠道疾病后一周，胸腺发育不良，细胞结构减少。萎缩伴随着细胞凋亡的增加。DKO小鼠的脾脏重量因红细胞蓄积而增加;然而，T和B细胞数量减少50%。相反，肠系膜淋巴结增大，淋巴细胞数量增加。来自DKO小鼠的T细胞具有记忆表型，并且对T细胞受体刺激反应迟钝。DKO小鼠的结肠炎与IL-2、干扰素-γ、IL-1 β、肿瘤坏死因子-α和IL-12的局部和高表达相关。DKO小鼠中的初级和次级淋巴器官由于胃肠道中的暴发性炎症而发生深刻改变。VDR表达是T细胞和其他免疫细胞控制IL-10 KO小鼠炎症所必需的。
The vitamin D receptor (VDR) is a nuclear receptor expressed in a number of different cells of the immune system. This study was performed to determine the effect of VDR deficiency on immune function and inflammation of the gastrointestinal tract in a model of inflammatory bowel disease, namely interleukin-10 (IL-10) knockout mice. IL-10 knockout mice were generated which either could or could not respond to vitamin D (double IL-10/VDR knockout; DKO). The distribution and function of lymphocytes in both the primary and secondary lymphoid organs were compared and determined as a function of the severity of intestinal inflammation. DKO mice had normal thymic development and peripheral T-cell numbers at 3 weeks of age, but a week after intestinal disease was detected the thymus was dysplastic with a reduction in cellularity. The atrophy was coupled with increased apoptosis. The spleen weight of DKO mice increased as a result of the accumulation of red blood cells; however, there was a 50% reduction in the numbers of T and B cells. Conversely, the mesenteric lymph nodes were enlarged and contained increased numbers of lymphocytes. The T cells from DKO mice were of a memory phenotype and were hyporesponsive to T-cell receptor stimulation. Colitis in the DKO mice was associated with local and high expression of IL-2, interferon-gamma, IL-1 beta, tumour necrosis factor-alpha and IL-12. The primary and secondary lymphoid organs in DKO mice are profoundly altered as a consequence of the fulminating inflammation in the gastrointestinal tract. VDR expression is required for the T cells and other immune cells to control inflammation in the IL-10 KO mice.