Skin Barrier and the Microbiome

皮肤屏障和微生物组

• 批准号: 8696590
• 负责人: Richard L Gallo
• 金额: $ 33.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-18 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8696590
• 关键词: Affect; Atopic Dermatitis; Bacteria; Basement membrane; Camping; Cells; Clinical; Communities; Cream; Cutaneous; Defect; Dermal; Dermis; Development; Elements; Epidermis; Epithelial; Equilibrium; Event; Functional disorder; Gene Expression Profile; Genus staphylococcus; Goals; Human; Immune; Immune response; Immune system; Immunity; Immunohistochemistry; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Kidney; Laboratories; Life; Lung; Measurement; Measures; Microbe; Molecular; Mus; Mutation; Myelogenous; Organ; Positioning Attribute; Production; RNA Sequences; Role; Severity of illness; Skin; Small Interfering RNA; Structure; Surface; TNF receptor-associated factor 1; Tail; Testing; Transgenes; Water; Work; antimicrobial peptide; cathelicidin; cell type; clinically relevant; commensal microbes; cytokine; fighting; filaggrin; immune activation; immunoregulation; keratinocyte; microbial; microbial community; microbiome; overexpression; pathogen; public health relevance; repaired; resistant strain; response; skin disorder

DESCRIPTION (provided by applicant): The surface commensal microbial community has been shown to influence the function and development of the immune system, thus potentially participating in the pathophysiology of several important diseases of the skin, gut, kidney and lung. With increased appreciation that normal microbial communities exist in equilibrium with, and in many cases benefit the host, recent work has sought to better understand the mechanisms by which we permit survival of our skin commensal microbiome and how the microbiome controls mammalian immune responses. We have discovered that it was wrong to assume that bacteria are normally totally separated from us by the epidermis. Strong evidence now shows that microbial communities are in an equilibrium across the basement membrane zone and populate the dermal stroma. These observations show that the surface microbiome is in direct contact with live cells in the dermis, and therefore is in a prime position to influence local and systemic immunity. Importantly, the observation that microbes enter the dermis is not evidence for infection, rather this findings show that products made by microbes are communicating with dermal cells. The overall goal of this proposal is to understand the elements of the skin barrier that regulate microbial entry into the dermis and begin to test the hypothesis that changes in the dermal microbial community result in altered cutaneous immune responses. Our aims are as follows: Aim 1: Understand the role of filaggrin in control of entry of the microbiome and immune modulation. Aim 2: Study how the function of the dermal microbiome is influenced by cathelicidin expression Aim 3: Characterize the dermal microbiome in Atopic Dermatitis before and after skin barrier therapy. Successful completion of these aims will provide new understanding of the skin immune system and can clarify the pathophysiology of inflammatory skin diseases such as atopic dermatitis.

描述（由申请人提供）：已显示表面共生微生物群落会影响免疫系统的功能和发育，因此有可能参与皮肤，肠，肾脏和肺的几种重要疾病的病理生理学。随着对正常微生物群落的平衡存在与宿主有益的均衡，最近的工作试图更好地了解我们允许皮肤相关微生物组生存的机制，以及微生物组如何控制哺乳动物的免疫反应。我们发现，假设细菌通常与表皮完全分离是错误的。现在，有力的证据表明，微生物群落处于整个基底膜区域的平衡，并填充了真皮基质。这些观察结果表明，表面微生物组与真皮中的活细胞直接接触，因此处于影响局部和系统性免疫的主要位置。重要的是，关于微生物进入真皮的观察并不是感染的证据，而是这一发现表明，由微生物制造的产品正在与真皮细胞通信。该提案的总体目标是了解调节微生物进入真皮的皮肤屏障的要素，并开始检验以下假设，即皮肤微生物群落的变化会导致皮肤免疫反应改变。我们的目的如下：目标1：了解菲尔格林在控制微生物组和免疫调节中的作用。 AIM 2：研究皮肤微生物组的功能如何受cathelicidin表达的影响AIM 3：在皮肤屏障治疗前后特征性皮肤炎中表征皮肤微生物组。这些目标的成功完成将为皮肤免疫系统提供新的了解，并可以阐明炎症性皮肤疾病（例如特应性皮炎）的病理生理。