哥本哈根大学：维生素D对激活免疫防御至关重要

University of Copenhagen: Vitamin D crucial to activating immune defenses

　

　

 

 

摘要：

科学家发现，维生素D对于激活我们的免疫防御至关重要，而且如果没有足够的维生素摄入量 - 免疫系统的杀伤细胞--T细胞 - 将无法对身体中的严重感染做出反应并对抗它们。研究小组发现，T细胞首先寻找维生素D以便激活，如果找不到足够的维生素D则无法完成激活过程。

 

完整的故事

 

　

图：当幼稚T细胞以T细胞受体（TCR）的识别出外来分子时，它会向维生素D受体（VDR）基因发送激活信号（1）。 VDR基因现在开始生产VDR（2）。 VDR结合T细胞中的维生素D（3）并被激活。与活化的VDR结合的维生素D回到细胞核并激活PLC-gamma1的基因（5）。产生PLC-gamma1（6）并且T细胞启动了。

图片来源：免疫学教授，Carsten Geisler

 

哥本哈根大学的科学家发现，维生素D对于激活我们的免疫防御至关重要，而且如果没有足够的维生素摄入量，免疫系统的杀伤细胞--T细胞 - 将无法应对并抵抗身体严重感染。

 

对于T细胞来检测和杀死外来病原体，如细菌或病毒团块，细胞必须首先被“触发”起作用，并从无活力和无害的免疫细胞“转化”成杀伤细胞，这些细胞准备寻找并消灭所有痕迹的外来病原体

 

研究人员发现，T细胞依赖维生素D来激活它们，如果血液中缺乏维生素D，它们将保持休眠状态，对于威胁的可能性“天真”。

 

 

启用激活的化学反应

 

为了使专门的免疫细胞（T细胞）保护身体免受危险的病毒或细菌的侵害，必须首先将T细胞暴露于外来病原体的痕迹。当它们被体内其他免疫细胞（称为巨噬细胞）呈现出病原体的可疑“细胞碎片”或“痕迹”时，就会发生这种情况。然后T细胞与片段结合并分裂并繁殖成数百个相同的细胞，这些细胞全部聚焦于相同的病原体类型。 T细胞经历的化学变化序列使它们既“敏感”又能够传递靶向免疫应答。

 

来自国际健康，免疫学和微生物学系的Carsten Geisler教授解释说，“当T细胞暴露于外来病原体时，它会扩展信号装置或称为维生素D受体的'天线'，用它来寻找维生素D这意味着T细胞必须含有维生素D或细胞的活化会停止。如果T细胞在血液中找不到足够的维生素D，它们就不会开始动员。“

 

成功激活的T细胞转化为两种类型的免疫细胞之一。它们或者成为杀伤细胞，它们会攻击并摧毁携带外来病原体痕迹的所有细胞，或者它们成为帮助免疫系统获得“记忆”的辅助细胞。辅助细胞向免疫系统发送信息，传递有关病原体的知识，以便免疫系统能够在下次遭遇时识别并记住它。 T细胞构成适应性免疫系统的一部分，这意味着它们通过教导免疫系统识别和适应不断变化的威胁来发挥作用。

　

　

 

 

激活和停用免疫系统

 

对于研究团队来说，确定维生素D在T细胞活化中的作用是一项重大突破。 “长期以来，科学家都知道维生素D对钙的吸收很重要，维生素也与癌症和多发性硬化症等疾病有关，但我们没有意识到维生素D对于实际激活免疫系统的重要性。我们现在知道了。“

 

科学家认为，这一发现提供了有关免疫系统的非常必要的信息，并将帮助他们调节免疫反应。这不仅对抗疾病，而且对处理身体的抗免疫反应和移植器官的排斥也很重要。活跃的T细胞以爆炸性的速度繁殖并且可以产生对身体具有严重后果的炎性环境。器官移植后，例如T细胞可以移植的器官作为“外来入侵者”攻击供体器官。在自身免疫性疾病中，过敏性T细胞将身体自身细胞的碎片误认为是外来病原体，导致身体对自身发动攻击。

 

研究小组还能够跟踪非活性T细胞向活性细胞转化的生化序列，从而能够在几个点进行干预以调节免疫应答。不活跃或“天真”的T细胞至关重要地既不含维生素D受体也不含特定分子（PLC-gamma1），使细胞能够传递抗原特异性反应。

 

Geisler教授的研究结果“继续帮助我们对抗传染病和全球流行病。它们在开发新疫苗时将特别有用，它们正是在训练我们的免疫系统作出反应和抑制身体自然防御的基础上发挥作用的。这很重要的情况 - 就像器官移植和自身免疫性疾病一样。“

 

大多数维生素D是皮肤暴露在阳光下的天然副产品。它也可以在鱼肝油，鸡蛋和脂肪鱼如鲑鱼，鲱鱼和鲭鱼中找到，或作为膳食补充剂。没有对维生素D的最佳日剂量进行确定的研究，但由于大部分人群的血液中维生素D浓度非常低，许多专家建议每天摄入25-50mg微克。

　

University of Copenhagen: Vitamin D crucial to activating immune defenses

　

　

　

Date: March 8, 2010

Source: University of Copenhagen

　

Summary:

Scientists have found that vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin - the killer cells of the immune system -- T cells -- will not be able to react to and fight off serious infections in the body. The research team found that T cells first search for vitamin D in order to activate and if they cannot find enough of it will not complete the activation process.

　

FULL STORY

　

　

　

　

Figure: When the naïve T cell recognizes foreign molecules with its T cell receptor (TCR) it sends activation signals (1) to the VDR gene. The VDR gene now starts the production of VDR (2). VDR binds vitamin D in the T cell (3) and becomes activated. Vitamin D bound to activated VDR goes back into the cell nucleus and activates the gene for PLC-gamma1 (5). PLC-gamma1 is produced (6) and the T cells can get started.

Credit: Professor of Immunology, Carsten Geisler

　

Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin, the killer cells of the immune system -- T cells -- will not be able to react to and fight off serious infections in the body.

 

For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be 'triggered' into action and 'transform' from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of a foreign pathogen.

 

The researchers found that the T cells rely on vitamin D in order to activate and they would remain dormant, 'naïve' to the possibility of threat if vitamin D is lacking in the blood.

 

 

Chemical Reaction that Enables Activation

 

In order for the specialized immune cells (T cells) to protect the body from dangerous viruses or bacteria, the T cells must first be exposed to traces of the foreign pathogen. This occurs when they are presented by other immune cells in the body (known as macrophages) with suspicious 'cell fragments' or 'traces' of the pathogen. The T cells then bind to the fragment and divide and multiply into hundreds of identical cells that are all focused on the same pathogen type. The sequence of chemical changes that the T cells undergo enables them to both be 'sensitized to' and able to deliver a targeted immune response.

 

Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology explains that "when a T cell is exposed to a foreign pathogen, it extends a signaling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D. This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won't even begin to mobilize. "

 

T cells that are successfully activated transform into one of two types of immune cell. They either become killer cells that will attack and destroy all cells carrying traces of a foreign pathogen or they become helper cells that assist the immune system in acquiring "memory." The helper cells send messages to the immune system, passing on knowledge about the pathogen so that the immune system can recognize and remember it at their next encounter. T cells form part of the adaptive immune system, which means that they function by teaching the immune system to recognize and adapt to constantly changing threats.

 

 

Activating and Deactivating the Immune System

 

For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. "Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn't realize is how crucial vitamin D is for actually activating the immune system -- which we know now. "

 

The discovery, the scientists believe, provides much needed information about the immune system and will help them regulate the immune response. This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs. Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. After organ transplants, e.g. T cells can attack the donor organ as a "foreign invader." In autoimmune disease, hypersensitive T cells mistake fragments of the body's own cells for foreign pathogens, leading to the body launching an attack upon itself.

 

The research team was also able to track the biochemical sequence of the transformation of an inactive T cell to an active cell, and thus would be able to intervene at several points to modulate the immune response. Inactive or 'naïve' T cells crucially contain neither the vitamin D receptor nor a specific molecule (PLC-gamma1) that would enable the cell to deliver an antigen specific response.

 

The findings, continues Professor Geisler "could help us to combat infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body's natural defenses in situations where this is important -- as is the case with organ transplants and autoimmune disease."

 

Most Vitamin D is produced as a natural byproduct of the skin's exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. No definitive studies have been carried out for the optimal daily dosage of vitamin D but as a large proportion of the population have very low concentrations of vitamin D in the blood, a number of experts recommend between 25-50mg micrograms a day.

https://www.sciencedaily.com/releases/2010/03/100307215534.htm

 

Story Source:

Materials provided by University of Copenhagen. Note: Content may be edited for style and length.

Journal Reference:

von Essen et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology, 2010; DOI: 10.1038/ni.1851