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Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate
The Journal of Immunology ( IF 3.6 ) Pub Date : 2021-11-01 , DOI: 10.4049/jimmunol.2001261
Benita C. Y. Tse 1 , Rachael A. Ireland 1, 2 , Jun Yup Lee 1 , Felix Marsh-Wakefield 1 , Lai Fong Kok 1 , Anthony S. Don 1, 3 , Scott N. Byrne 1, 2
Affiliation  

Systemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Exposure of C57BL/6 mice to doses of UV known to suppress systemic autoimmunity led to the accumulation of cells within the skin-draining lymph nodes and away from non–skin-draining lymph nodes. Transfer of CD45.1+ cells from nonirradiated donors into CD45.2+ UV-irradiated recipients resulted in preferential accumulation of donor naive T cells and a decrease in activated T cells within skin-draining lymph nodes. A single dose of immune-suppressive UV was all that was required to cause a redistribution of naive and central memory T cells from peripheral blood to the skin-draining lymph nodes. Specifically, CD69-independent increases in sphingosine-1-phosphate (S1P) receptor 1–negative naive and central memory T cells occurred in these lymph nodes. Mass spectrometry analysis showed UV-mediated activation of sphingosine kinase 1 activity, resulting in an increase in S1P levels within the lymph nodes. Topical application of a sphingosine kinase inhibitor on the skin prior to UV irradiation eliminated the UV-induced increase in lymph node S1P and T cell numbers. Thus, exposure to immunosuppressive UV disrupts T cell recirculation by manipulating the S1P pathway.



中文翻译:

暴露于全身免疫抑制性紫外线辐射通过 Sphingosine-1-Phosphate 改变 T 细胞再循环

系统性抑制适应性免疫反应是紫外线辐射导致皮肤癌发展的主要方式。免疫抑制也可能解释紫外线如何预防某些自身免疫性疾病,例如多发性硬化症。然而,紫外线介导的全身免疫抑制的机制尚不清楚。将 C57BL/6 小鼠暴露于已知可抑制全身性自身免疫的紫外线剂量下,会导致细胞在皮肤引流淋巴结内和远离非皮肤引流淋巴结的积聚。将 CD45.1 +细胞从未照射过的供体转移到 CD45.2 +紫外线照射的受体导致供体幼稚 T 细胞的优先积累和皮肤引流淋巴结内活化 T 细胞的减少。只需要一剂免疫抑制性紫外线,就可以导致幼稚和中枢记忆 T 细胞从外周血重新分布到皮肤引流淋巴结。具体而言,在这些淋巴结中发生了 1-磷酸鞘氨醇 (S1P) 受体 1 阴性初始和中枢记忆 T 细胞的 CD69 非依赖性增加。质谱分析显示紫外线介导的鞘氨醇激酶 1 活性激活,导致淋巴结内 S1P 水平增加。在紫外线照射前在皮肤上局部应用鞘氨醇激酶抑制剂可消除紫外线引起的淋巴结 S1P 和 T 细胞数量的增加。因此,

更新日期:2021-10-19
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