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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

基本信息

批准号：
10023927
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
项目类别：
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/10023927
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 Epithelium 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

项目摘要

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/文摘