1,25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis
1,25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis
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DOI：
10.1002/eji.201040632
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发表时间：
2011-03-01
影响因子：
5.4
通讯作者：
Hayes, Colleen E.
中科院分区：
文献类型：
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作者：
Mayne, Christopher G.;Spanier, Justin A.;Hayes, Colleen E.
多发性硬化（MS）是一种无法治愈的自身免疫性神经退行性疾病。环境因素可能是MS预防和治疗的关键。MS患病率和严重程度随着阳光照射和维生素D-3供应的增加而降低，支持我们的假设，即阳光依赖性激素1，25-二羟基维生素D-3（1，25（OH）（2）D-3）抑制MS中的自身免疫T细胞反应。此外，1，25-（OH）（2）D-3抑制并逆转实验性自身免疫性脑脊髓炎（EAE），一种MS模型。在这里，我们研究了1，25-（OH）（2）D-3是否通过T淋巴细胞中的维生素D受体（VDR）抑制EAE。使用仅在放射敏感性造血细胞或放射抗性非造血细胞中具有破坏的VDR的骨髓嵌合小鼠，我们发现造血细胞VDR功能对于1，25-（OH）（2）D-3抑制EAE是必需的。此外，条件靶向实验表明，T细胞中的VDR功能是必要的。在这些研究中，1，25-（OH）（2）D-3和T细胞特异性VDR靶向均不影响外周或CNS中的CD 4（+）Foxp 3（+）T细胞比例。这些数据支持1，25-（OH）（2）D-3直接作用于致病性CD 4（+）T细胞以抑制EAE的模型。
Multiple sclerosis (MS) is an incurable autoimmune neurodegenerative disease. Environmental factors may be key to MS prevention and treatment. MS prevalence and severity decrease with increasing sunlight exposure and vitamin D-3 supplies, supporting our hypothesis that the sunlight-dependent hormone, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), inhibits autoimmune T-cell responses in MS. Moreover, 1,25-(OH)(2)D-3 inhibits and reverses experimental autoimmune encephalomyelitis (EAE), an MS model. Here, we investigated whether 1,25-(OH)(2)D-3 inhibits EAE via the vitamin D receptor (VDR) in T lymphocytes. Using bone marrow chimeric mice with a disrupted VDR only in radiosensitive hematopoietic cells or radio-resistant non-hematopoietic cells, we found that hematopoietic cell VDR function was necessary for 1,25-(OH)(2)D-3 to inhibit EAE. Furthermore, conditional targeting experiments showed that VDR function in T cells was necessary. Neither 1,25-(OH)(2)D-3 nor T-cell-specific VDR targeting influenced CD4(+)Foxp3(+) T-cell proportions in the periphery or the CNS in these studies. These data support a model wherein 1,25-(OH)(2)D-3 acts directly on pathogenic CD4(+) T cells to inhibit EAE.