Elucidating the role of type 2 immunity in skin homeostasis

项目摘要/摘要 这份提案描述了一项为期5年的研究和职业发展计划，该计划将使罗伯托·里卡多博士 冈萨雷斯将实现他的长期目标，成为一名独立资助的内科医生兼科学家，研究如何 组织驻留的先天免疫细胞与组织生态位在发育、内稳态和 疾病。里卡多·冈萨雷斯博士是加州大学旧金山分校皮肤科助理教授。 弗朗西斯科。这位候选人长期以来一直有兴趣研究2型免疫反应是如何改变的 疾病。他最近发表了一项研究，描述了一种定义先天2型的组织组织转录组 来自不同器官的淋巴样细胞(ILC2s)，强调这些细胞是2型细胞因子的关键来源 在皮肤和其他独立于微生物区系的组织中。更多的初步数据表明ILC2已经铺设 在皮肤发育的早期，它们的功能与上皮功能是耦合的。长期目标 这项拟议的研究的目的是了解2型免疫反应在维持 并将检验2型免疫对维持最佳皮肤至关重要的假说 组织功能和动态平衡。为了研究这一点，他提出了以下三个补充 评估2型免疫如何影响皮肤动态平衡的方法。目标1将阐明ILC2和ILC2s如何 2型免疫对于维持皮肤的正常功能和上皮干细胞的健康至关重要。目标2将 剖析2型免疫系统在发育过程中如何在组织中设定，以及这是如何影响组织的 动态平衡和炎症。目标3，将开发新的工具，允许时空控制 ILC2和其他淋巴细胞群体的贩运和基因组编辑。在这项研究中，候选人将使用 机械研究和尖端技术的结合，将为他提供更多 培训和专业知识，成为一名独立的调查员。在理查德·洛克斯利博士的指导下， 一位过敏性免疫专家，与他的多学科科学咨询委员会合作， 候选人、导师和科学顾问为里卡多·冈萨雷斯博士制定了职业发展计划 为了获得最先进的免疫学和成像研究技术、生物统计学、 上皮细胞和干细胞生物学，以及科学交流。总体而言，拟议的实验将 扩大我们对2型免疫如何影响皮肤动态平衡的基本理解，特别是 将有助于揭示这一免疫轴的非免疫新角色。

Project Summary/Abstract This proposal describes a 5-year research and career development plan that will allow Dr. Roberto Ricardo Gonzalez to achieve his long-term goal of becoming an independently funded physician-scientist studying how tissue-resident innate immune cells coordinate with the tissue niche during development, homeostasis, and disease. Dr. Ricardo Gonzalez is an assistant professor of dermatology at the University of California, San Francisco. The candidate has a long-standing interest in studying how type 2 immune responses are altered in disease. He recently published a study describing a tissue-organizing transcriptome defining type 2 innate lymphoid cells (ILC2s) from distinct organs, that emphasized these cells as critical sources of type 2 cytokines in the skin and other tissues independent of the microbiota. Additional preliminary data suggest ILC2s are laid out in the skin early in development, and that their function is coupled to epithelial function. The long-term goal of the proposed study is to understand the fundamental role of type 2 immune responses in maintaining epithelial health and will test the hypothesis that type 2 immunity is critical in the maintenance of optimal skin tissue function and homeostasis. To investigate this, he proposes the following three complementary approaches to evaluate how type 2 immunity influences skin homeostasis. Aim 1 will elucidate how ILC2s and type 2 immunity are critical for maintaining proper function of the skin and epithelial stem cell fitness. Aim 2 will dissect how the type 2 immune tone is set in tissues during development and how this influences tissue homeostasis and inflammation. Aim 3, will develop new tools that will allow for spatiotemporal control of trafficking and genome editing of ILC2s and other lymphocyte populations. In this study, the candidate will use a combination of mechanistic studies and cutting-edge technologies that will provide him with additional training and expertise to become an independent investigator. Under the mentorship of Dr. Richard Locksley, an expert in allergic immunity, and in collaboration with his multidisciplinary scientific advisory committee, the candidate, mentor and scientific advisors have developed a career development plan for Dr. Ricardo Gonzalez to gain additional experience in state of the art immunology and imaging research techniques, biostatistics, epithelial and stem cell biology, and scientific communication. Overall, the experiments proposed would expand our fundamental understanding of how type 2 immunity influences skin homeostasis and specifically will shed light into the non-immune novel roles of this immune axis.