Role of the Mast Cell Product Histamine in Ultraviolet Radiation Induced Systemic Immunomodulation

紫外线辐射对皮肤的有害影响，如阳光照射的例子，已得到很好的认识：晒伤、皮肤过早老化和诱发皮肤癌。事实上，皮肤癌是澳大利亚最常见的癌症。现在越来越多的人认识到紫外线辐射可以改变免疫系统。这与皮肤癌的发展特别相关：免疫系统的改变对于紫外线诱导的癌症的发展至关重要。此外，完整的免疫系统能够排斥绝大多数紫外线诱发的皮肤癌。紫外线辐射对免疫系统的这种影响可能与其他疾病有关。它可能会改变一些感染的过程，改变身体对疫苗接种的反应方式，也可能在一些免疫相关疾病中发挥作用，如多发性硬化症。这些超出可见光的波长是如何影响免疫系统的，这是这个项目的主题。我们知道，紫外线辐射只能穿透皮肤很短的一段路，但却可以对免疫系统产生广泛的影响。到目前为止，我们的研究已经表明，位于皮肤表面下方的一种特殊细胞类型--真皮肥大细胞--是必不可少的。我们还展示了对紫外线照射的早期反应的一些复杂性--皮肤最外层的一种化学物质(顺式尿毒酸)和皮肤中的神经都有作用。重要的是，抗组胺药物可以抑制紫外线对免疫反应的影响。更多的证据还表明，肥大细胞的产物组胺在紫外线照射后的免疫变化中发挥了关键作用。我们的研究旨在描述组胺对免疫反应发展的中心细胞树突状细胞的影响，并在实验模型中确定这种影响的机制。在与英国研究人员的合作中，我们将进一步表征肥大细胞在人体紫外线免疫变化中的作用。

The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise able to reject the great majority of UV-induced skin cancers. This effect of UV radiation on the immune system may be relevant to other diseases. It may alter the course of some infections, change the way the body responds to vaccination, and may also have a role in some immune-related diseases such as multiple sclerosis. How it is that these wavelengths just beyond visible light can affect the immune system is the subject of this project. We know that UV radiation can penetrate only a short way into the skin, yet can have widespread effects on the immune system. Our research to now has shown that a particular cell type sitting just below the surface of skin, the dermal mast cell, is essential. We've also demonstrated some of the complexity of the early response to UV exposure - both a chemical (cis-urocanic acid) in the very outermost layer of skin, and nerves in the skin, have roles. Importantly, anti-histamines can inhibit UV effects on immune responses. Additional lines of evidence also point to histamine, a product of mast cells, as playing a pivotal role in the immune alterations following UV exposure. Our research aims to characterise the effects of histamine on cells central to the development of immune responses, known as dendritic cells, and define the mechanisms of the effect in experimental models. In collaboration with researchers in the UK, we will further characterise the role of mast cells in UV alterations to immunity in humans.