Elucidating the role of type 2 immunity in skin homeostasis

阐明 2 型免疫在皮肤稳态中的作用

• 批准号: 10472581
• 负责人: ROBERTO RAFAEL RICARDO-GONZALEZ
• 金额: $ 17.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10472581
• 关键词: Advisory Committees; Allergic; Allergic Disease; Atopic Dermatitis; Biometry; California; Cell Aging; Cell Maintenance; Cells; Cellular biology; Clinical; Collaborations; Communication; Communities; Coupled; Cytokine Signaling; Data; Dermatology; Development; Development Plans; Disease; Eczema; Enterobacteria phage P1 Cre recombinase; Epithelial; Extrinsic asthma; Funding; Genetic; Genetic Transcription; Genome engineering; Goals; Hair; Hair Removal; Hair follicle structure; Health; Homeostasis; Hypersensitivity; Image; Immune; Immune response; Immunity; Immunology; Inflammation; Inflammatory; Interleukin-13; Interleukin-18; Interleukin-4; Interleukin-5; Interleukins; Knowledge; Light; Lung; Lymphocyte; Lymphoid Cell; Maintenance; Mentors; Mentorship; Modeling; Molecular; Mouse Strains; Mus; Natural regeneration; Organ; Pathogenesis; Pathogenicity; Pathologic; Pathology; Physicians; Play; Population; Positioning Attribute; Publishing; Research; Research Design; Research Personnel; Research Technics; Role; San Francisco; Scientist; Shapes; Signal Transduction; Skin; Skin Tissue; Source; Structure of parenchyma of lung; Technology; Testing; Tissue Model; Tissues; Training; Universities; Work; allergic response; career development; cell type; cellular engineering; cytokine; epithelial stem cell; experience; experimental study; fitness; genome editing; in vivo; insight; interest; microbiota; mouse model; multidisciplinary; new therapeutic target; novel; optogenetics; postnatal development; preservation; professor; repaired; research and development; response; skin organogenesis; spatiotemporal; stem; stem cell biology; stem cells; tissue injury; tissue repair; tissue-repair responses; tool; trafficking; transcriptome

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.

项目总结/摘要 该提案描述了一个5年的研究和职业发展计划，将允许罗伯托里卡多博士 冈萨雷斯实现他的长期目标，成为一个独立资助的医生，科学家研究如何 组织驻留的先天免疫细胞在发育、稳态和免疫应答过程中与组织小生境协调。 疾病里卡多·冈萨雷斯博士是加州大学旧金山分校的皮肤病学助理教授。 弗朗西斯科。这位候选人长期以来一直对研究2型免疫反应如何在体内改变感兴趣。 疾病他最近发表了一项研究，描述了一种组织组织转录组， 来自不同器官的淋巴样细胞（ILC 2），强调这些细胞是2型细胞因子的关键来源 在皮肤和其他组织中独立于微生物群。额外的初步数据表明， 在皮肤发育的早期，它们的功能与上皮功能相结合。远景目标 这项研究的目的是了解2型免疫反应在维持免疫系统中的基本作用。 上皮健康，并将测试假设2型免疫是至关重要的，在维持最佳的皮肤 组织功能和体内平衡。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稳态的方法。目标1将阐明ILC 2和 2型免疫对于维持皮肤的正常功能和上皮干细胞的适应性至关重要。目标2将 剖析在发育过程中，2型免疫调节是如何在组织中设定的，以及这如何影响组织 稳态和炎症。目标3，将开发新的工具，将允许时空控制 ILC 2和其他淋巴细胞群体的运输和基因组编辑。在这项研究中，候选人将使用 机械研究和尖端技术的结合，将为他提供额外的 培训和专业知识，成为独立调查员。在理查德·劳克斯利博士的指导下， 过敏性免疫专家，并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 在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。总的来说，拟议的实验将 扩展我们对2型免疫如何影响皮肤稳态的基本理解， 将揭示这个免疫轴的非免疫新作用。