Glucocorticoids and development of the immune system

糖皮质激素和免疫系统的发育

• 批准号: RGPIN-2019-04837
• 负责人: Soma, Kiran
• 金额: $ 3.42万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714476
• 关键词: Glucocorticoids; development; immune; system

Stress has major effects on the immune system in all vertebrate animals. In particular, early-life stress can “program” the immune system and have enduring consequences that last into adulthood. Glucocorticoids are steroid hormones that increase in response to environmental stressors. These hormones are secreted by the adrenal glands and, via the blood, reach their targets (for example, the thymus and bone marrow, where important immune cells develop). In addition, recent research shows that glucocorticoids are locally produced within the immune organs themselves, particularly early in life. This surprising discovery raises many interesting and important questions. This research project focuses on the local synthesis of glucocorticoids in immune organs during early development. In particular, how are local glucocorticoid levels regulated by environmental stressors, immune challenges, internal physiological factors, and the microbiome? How do these local glucocorticoids act on immune cells? Do local glucocorticoids have enduring or transient effects? To answer these major questions about the basic biology of this system, this project will integrate multiple cutting-edge techniques, including molecular biology, microbiome bioinformatics, mass spectrometry imaging, and liquid chromatography tandem mass spectrometry. The answers to these important questions will help us understand how stress affects the immune systems of young and adult animals. In addition, the advances in high-throughput mass spectrometry will accelerate endocrine research worldwide and equip future Canadian scientists with key technical skills. The fundamental knowledge gained from this project will have broad impacts on a variety of disciplines, including endocrinology, physiology, neuroscience, microbiology, immunology, and analytical chemistry.

压力对所有脊椎动物的免疫系统都有重大影响。特别是，早期生活压力可以“编程”免疫系统，并产生持续到成年的持久后果。糖皮质激素是一种类固醇激素，在环境压力下会增加。这些激素由肾上腺分泌，通过血液到达它们的目标（例如，胸腺和骨髓，重要的免疫细胞在那里发育）。此外，最近的研究表明，糖皮质激素是在免疫器官本身局部产生的，特别是在生命早期。这一惊人的发现提出了许多有趣而重要的问题。 该研究项目的重点是早期发育期间免疫器官中糖皮质激素的局部合成。特别是，局部糖皮质激素水平如何受环境压力、免疫挑战、内部生理因素和微生物组的调节？这些局部糖皮质激素如何作用于免疫细胞？局部糖皮质激素的作用是持久的还是短暂的？为了回答这些关于该系统基础生物学的主要问题，该项目将整合多种前沿技术，包括分子生物学，微生物组生物信息学，质谱成像和液相色谱串联质谱。 这些重要问题的答案将帮助我们了解压力如何影响年轻和成年动物的免疫系统。此外，高通量质谱的进步将加速全球内分泌研究，并为未来的加拿大科学家提供关键技术技能。从这个项目中获得的基础知识将对各种学科产生广泛的影响，包括内分泌学，生理学，神经科学，微生物学，免疫学和分析化学。