MECHANISMS OF UV-INDUCED IMMUNE SUPPRESSION

紫外线诱导的免疫抑制机制

• 批准号: 2390923
• 负责人: FAITH M STRICKLAND
• 金额: $ 10.38万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-10 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2390923
• 关键词: antigen presenting cell; artificial immunosuppression; contact dermatitis; cytokine; delayed hypersensitivity; enzyme linked immunosorbent assay; flow cytometry; immunofluorescence technique; immunosuppression; interleukin 10; interleukin 12; laboratory mouse; light adverse effect; neoplasm /cancer transplantation; photoprotection; photoprotective agent; plant extracts; radiation related neoplasm /cancer; skin neoplasms; suppressor T lymphocyte; tissue /cell culture; topical drug application; tumor necrosis factor alpha; ultraviolet radiation

Epicutaneous exposer to ultraviolet (UV) radiation suppresses T cell- mediated immune responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Immune suppression by UV radiation is mediated by multiple, complex, and interacting mechanisms. Recent studies indicate the suppression is triggered by DNA damage followed by production of immunosuppressive cytokines, loss of antigen presenting cells (APC) from the skin, alteration of the functions of remaining APC, and induction of antigen-specific suppressor T cells. However, the regulation nd interaction of these APC, and induction of antigen-specific suppressor T cells. However, the regulation and interaction of these APC and cytokine pathways are unclear and appears to be different for contact hypersensitivity (CHS) reactions to allergens in skin and delayed type hypersensitivity (DTH) reactions to microorganisms. We have recently shown that crude extracts of Aloe barbadensis gel protects CHS and DTH responses against suppression by UV radiation. Because Aloe extract provides broad protection for immune responses that are abrogated by UN by different mechanisms, it may act as a central controlling point in suppression. Alternatively Aloe may contain several agents that act on CHS and DTH separately. Furthermore, Aloe is chemically distinct from antibodies, cytokines, or other agents that have been used to probe suppression pathway induced by UV radiation, and it may be acting by a novel mechanism(s). We will test these hypotheses by exposing mice to UV radiation and examining the effect of Aloe treatment on the production of the regulatory cytokines TNF-alpha, IL-10, and Il-12 in cultured keratinocyte cell liens and in skin. We will investigate whether protection of CHS and DTH responses is mediated separately by different components in Aloe. We will also examine the effect of Aloe on the function of APC from the draining lymph nodes using the murine model of CHS response to the hapten fluorescein isothiocyanate, and the DTH response to Candida albicans. In addition, we propose to investigate the ability of Aloe to preserve immunity to UV-induced skin cancers. Clarification of the relationship of the CHS and DTH models to cutaneous tumor immunity may permit the design of therapeutic agents that are more effective in protecting humans against the development of skin cancer.

紫外线（UV）辐射的表皮吸收抑制T细胞- 介导的对皮肤中遇到的抗原的免疫应答， 在实验室动物中高免疫原性皮肤癌的生长。 紫外线辐射引起的免疫抑制是由多种、复杂的 互动机制 最近的研究表明， 由DNA损伤引发，随后产生免疫抑制剂， 细胞因子，皮肤抗原呈递细胞（APC）的丢失， 剩余APC的功能，以及诱导抗原特异性 抑制性T细胞 然而，这些APC的调节和相互作用， 和抗原特异性抑制性T细胞的诱导。 但 这些APC和细胞因子途径的调节和相互作用尚不清楚 接触性超敏反应（CHS）似乎与 皮肤过敏原和迟发型超敏反应（DTH） 微生物的 我们最近发现，库拉索芦荟凝胶的粗提物可以保护 CHS和DTH对UV辐射抑制的响应。 因为芦荟 提取物为被废除的免疫反应提供广泛的保护 通过不同的机制，它可以作为一个中央控制点， 镇压 另外，芦荟可能含有几种作用于CHS的药剂 和DTH分开。 此外，芦荟在化学上不同于 抗体、细胞因子或其他用于探测 抑制途径诱导的紫外线辐射，它可能是通过一个 新机制。 我们将通过将小鼠暴露于紫外线辐射来测试这些假设， 检查芦荟处理对调节性蛋白质的产生的影响， 培养的角质形成细胞系中的细胞因子TNF-α、IL-10和IL-12 在皮肤上。 我们会研究保护社区卫生服务和直接到户的 反应分别由芦荟中的不同成分介导。 我们将 并从引流液中检测芦荟对APC功能的影响 使用CHS对半抗原应答的鼠模型的淋巴结 异硫氰酸荧光素和对白色念珠菌的DTH反应。 在 此外，我们建议研究芦荟的保存能力， 对紫外线引起的皮肤癌的免疫力。 澄清与 皮肤肿瘤免疫的CHS和DTH模型可能允许设计 更有效地保护人类免受 皮肤癌的发展。