Epigenetic regulation of sexually dimorphic immune responses in keratinocytes

角质形成细胞中性二态性免疫反应的表观遗传调控

• 批准号: 10215655
• 负责人: Johann Eli Gudjonsson
• 金额: $ 20.59万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-05 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215655
• 关键词: Address; Affect; Area; Autoimmune Diseases; Autoimmunity; Biological; Biological Response Modifiers; Cell Adhesion; Cells; Chromatin; Chromosomes; Clustered Regularly Interspaced Short Palindromic Repeats; Critical Pathways; DNA Methylation; Data; Development; Disease; Disease susceptibility; Epidermis; Epigenetic Process; Female; Future; Gene Expression; Genes; Genetic Transcription; Goals; Gonadal Steroid Hormones; Histones; Human; Immune; Immune System Diseases; Immune Targeting; Immune response; Immunologics; Immunotherapy; In Vitro; Infection; Infectious Skin Diseases; Inflammatory; Inflammatory Response; Influentials; Interferon Type I; Knowledge; Lead; Link; Mediating; Modification; Mus; Mycoses; Ontology; Organ; Pathologic; Phenotype; Physiological; Precision therapeutics; Predisposition; Preventive measure; Process; Promoter Regions; Regulator Genes; Sex Bias; Sex Chromosomes; Sex Differences; Shapes; Skin; Stimulus; Systemic Lupus Erythematosus; Testing; Therapeutic; Tissues; Woman; Work; autosome; base; chromatin immunoprecipitation; direct application; epigenetic marker; epigenetic regulation; epigenetic variation; histone modification; immune activation; keratinocyte; male; men; new therapeutic target; novel; promoter; response; sex; sexual dimorphism; skin disorder; therapeutic target; therapy development; transcriptomics

PROJECT SUMMARY Dysregulation of inflammatory responses are observed in a variety of cutaneous diseases, including autoimmune diseases and infections. A striking feature of these conditions is sexual dimorphism relating to the differential incident rates of these diseases between women and men. Understanding the underlying mechanism for the sex-biased inflammatory responses can point towards previously unappreciated pathways that are critical in regulating immune responses, and therefor can lead to development of sex-specific therapeutic approaches. Current data on the effect of sex-hormones and sex-chromosome regulatory genes insufficiently explain these biologic differences between men and women. We have recently identified differential epigenetic modifications between male and female keratinocytes, setting the stage for our hypothesis that sexually dimorphic epigenetic modifications in keratinocytes affect immune gene transcription and responses. The objective of this project is to identify and target epigenetic modifications that drive sexually dimorphic immune responses, allowing future development of precision therapies for inflammatory skin disorders. Upon the successful completion of this project, we will have characterized epigenetic differences between skin cells in women and men, determined the contribution of these sex-biased epigenetic modifications to immunological responses, and assessed whether they could serve as therapeutic targets for future treatment of immune mediated skin disorders.

项目概要 在多种皮肤疾病中观察到炎症反应失调，包括 自身免疫性疾病和感染。这些情况的一个显着特征是与 这些疾病在女性和男性之间的发病率存在差异。了解底层 性别偏向炎症反应的机制可能指向以前未被认识到的途径 这对于调节免疫反应至关重要，因此可能导致性别特异性的发展 治疗方法。关于性激素和性染色体调控基因影响的最新数据 不足以解释男性和女性之间的这些生物学差异。我们最近确定了 男性和女性角质形成细胞之间的差异表观遗传修饰，为我们的 角质形成细胞的性二态性表观遗传修饰影响免疫基因的假设 转录和反应。该项目的目标是识别和靶向表观遗传修饰 驱动性别二态性免疫反应，从而允许未来开发精准疗法 炎症性皮肤病。该项目成功完成后，我们将总结出 女性和男性皮肤细胞之间的表观遗传差异决定了这些性别偏见的贡献 对免疫反应的表观遗传修饰，并评估它们是否可以作为治疗 未来治疗免疫介导的皮肤病的目标。