Acne: a disease of lipid metabolism, microbiome and the immune response

摘要/项目摘要 总括 加州大学洛杉矶分校/加州大学洛杉矶分校痤疮研究翻译中心(Acne Cort)的总体目标是将 在微生物学、脂代谢和免疫学的不同方面拥有专业知识的科学家从事 微生物区系、脂类代谢与宿主免疫相互作用的翻译研究 对粉刺的反应。痤疮皮肤杆菌是毛脂腺单位(PSebU)的优势细菌，最初的 痤疮皮损形成的部位，被认为是导致痤疮的关键因素之一。 痤疮的发病机制。加州大学洛杉矶分校/加州大学圣地亚哥分校的研究项目是基于我们最近的发现，使用 转录组学、元基因组学和脂质组学，确立了将这些不同的生物联系在一起的目标 反应转化为可能解释粉刺发病机制的模型。加州大学洛杉矶分校/加州大学圣地亚哥分校研究项目 (加洛·莫德林)，《痤疮：一种脂代谢、微生物群和免疫反应的疾病》，将首先聚焦于 TREM2巨噬细胞和成脂成纤维细胞在痤疮发病机制中作用的研究我们的 使用单细胞rna测序(scrna-seq)和空间测序的初步数据鉴定了这些 两种细胞群在痤疮皮损中代表过多，基因程序反映了它们与脂质变化的联系 新陈代谢。项目调查人员将获得痤疮活检样本(HATA，KIM)，然后解决链接 痤疮皮损对微生物群的免疫反应与脂类代谢之间的关系。研究项目 将得到加州大学洛杉矶分校生物信息学核心(Pellegrini，Yang)的支持，以分析scRNA-seq和空间-seq 痤疮皮损，UCSD微生物学和元基因组学核心(Galo，O‘Neill)分离和鉴定C. 痤疮菌株，以及活检标本和关键细胞类型的脂质组学分析(本辛格，加州大学洛杉矶分校) 体外培养。最终，生物信息学核心将使用合并基因组学来结合转录组学的数据， 元基因组学和脂质组学创建了痤疮发病机制的网络模型。行政核心 将通过以下方式促进项目之间的研究互动：i)研究研讨会、丰富计划 和咨询委员会会议；ii)扩大研究基础的试点和可行性项目计划；以及，iii) 计划利用加州大学洛杉矶分校/加州大学洛杉矶分校的资源和环境，包括核心设施、加州大学洛杉矶分校和加州大学洛杉矶分校 临床和转化科学奖(CTSA)计划中心以及 医学和研究生，博士后研究员，皮肤科实习生和初级教员。建议数 研究将为脂代谢和皮肤微生物群如何塑造皮肤免疫提供新的见解 有助于炎症的反应，有可能干预皮肤病。

ABSTRACT / PROJECT SUMMARY Overall The overall goal of the UCLA/UCSD Acne Center for Research Translation (Acne CORT) is to bring together scientists with expertise in different aspects of microbiology, lipid metabolism and immunology to engage in translational research to study the interaction between the microbiota, lipid metabolism and the host immune response in acne. Cutibacterium acnes is the dominant bacterium of the pilosebaceous unit (PSebU), the initial site where acne lesions develop, and is considered to be one of the key contributing factors in the pathogenesis of acne. The UCLA/UCSD Research Project is based on our recent findings using transcriptomics, metagenomics and lipidomics, establishing the goal to link together these diverse biologic responses into a model that may explain the pathogenesis of acne. The UCLA/UCSD Research Project (Modlin, Gallo), “Acne: a disease of lipid metabolism, microbiome and the immune response”, will initially focus studies on the role of TREM2 macrophages and adipogenic fibroblasts in the pathogenesis of acne. Our preliminary data using from single cell RNA-sequencing (scRNA-seq) and spatial-sequencing identified these two cell populations as over-represented in acne lesions, with gene programs reflecting their link to altered lipid metabolism. The project investigators will obtain acne biopsy specimens (Hata, Kim), then address the link between the immune response in acne lesions to the microbiome and lipid metabolism. The Research Project will be supported by a UCLA Bioinformatics Core (Pellegrini, Yang) to analyze scRNA-seq and spatial-seq of acne lesions, a UCSD Microbiology and Metagenomics Core (Gallo, O'Neill) to isolate and characterize C. acnes strains, and lipidomics analysis (Bensinger, UCLA) of biopsy specimens and key cell types derived in vitro. Ultimately, the Bioinformatics Core will use mergeomics to combine data from transcriptomics, metagenomics and lipidomics to create a network model of the pathogenesis of acne. The Administrative Core will facilitate research interactions between the projects with: i) research seminars, an Enrichment Program and Advisory Board meeting; ii) a Pilot and Feasibility Project Program to extend the research base; and, iii) plans to utilize the resources and environment at UCLA/UCSD including core facilities, the UCLA and UCSD Clinical and Translational Science Awards (CTSA) Program Centers as well as the mentoring programs for medical and graduate students, postdoctoral fellows, dermatology trainees and junior faculty. The proposed studies will provide new insights into how lipid metabolism and the skin microbiome shape cutaneous immune responses contributing to inflammation, with the potential for intervention in skin disease.