Preferential perinatal thymic programming of skin-homing innate lymphoid cells in early establishment of skin homeostasis

皮肤归巢先天淋巴细胞的围产期胸腺优先编程在皮肤稳态的早期建立中

• 批准号: 9323092
• 负责人: NA XIONG
• 金额: $ 38.3万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323092
• 关键词: Alpha Cell; Applications Grants; Birth; Cells; Communicable Diseases; Dermatitis; Development; Disease; Environment; Epithelial; Epithelial Cells; Face; Foundations; Functional disorder; Future; GPR2 gene; Generations; Goals; Homeostasis; Homing; Immune; Immune response; Immune system; Immunity; Immunization; Incidence; Inflammation; Inflammatory; Ligands; Lymphocyte; Lymphoid; Lymphoid Cell; Maintenance; Molecular; Mus; Neonatal; Newborn Infant; Organ; Perinatal; Play; Population; Positioning Attribute; Process; Property; Psoriasis; Public Health; Regulation; Regulatory T-Lymphocyte; Role; Signal Pathway; Signal Transduction; Skin; Stromal Cells; Symbiosis; Thymus Gland; Tissues; Vaccines; assault; base; chemokine receptor; commensal microbes; design; environmental agent; fetal; microbial; migration; mouse model; notch protein; novel; programs; skin disorder; therapeutic development; therapeutic target; transcription factor

Summary The skin is the outmost epithelial tissue of a body that is under frequent assaults of environmental agents. To protect against the assaults and maintain the local tissue integrity, immune cells need to be properly positioned in the skin. A group of immune cells, namely innate lymphoid cells (ILCs), are preferentially localized in the skin where they function as the first line of defense but can also contribute to the skin inflammatory diseases such as topical dermatitis and psoriasis when dysregulated. The goal of this project is to understand how the establishment of ILCs in the skin is regulated for the immune protection and homeostasis of the skin during early fetal/neonatal stages. Our preliminary study discovered a novel process that directs fetal/newborn thymic NK1.1+ ILCs to acquire a skin-homing property for their specific localization into the skin. Considering that the skin is under assaults of environmental agents immediately after the birth, we propose that the preferential generation of fetal/neonatal thymic innate lymphocytes with skin-homing properties represents a developmentally programmed process that targets innate lymphocyte populations to the skin for the “border” protection in the neonatal stage and helps establish the immune homeostasis. In this application, we propose to dissect molecular mechanisms regulating the preferential acquisition of the skin-homing property by fetal thymic innate lymphocytes and its roles in promoting the establishment of skin immune homeostasis.

摘要 皮肤是身体最外层的上皮组织，经常受到 环保人员。以保护身体免受攻击，并保持局部组织 完整性，免疫细胞需要在皮肤中适当地定位。一群免疫的 细胞，即先天淋巴样细胞(ILCs)，优先定位于皮肤中 它们起着第一道防线的作用，但也会导致皮肤发炎 疾病，如局部皮炎和牛皮癣当调节失调时。这样做的目的是 项目的目的是了解皮肤中ILC的建立是如何为 胎儿/新生儿早期皮肤的免疫保护和动态平衡。我们的 初步研究发现了一种引导胎儿/新生儿胸腺NK1.1+的新过程 ILC为其特定的皮肤定位获得皮肤归巢特性。 考虑到皮肤在紧随其后受到环境因素的攻击 出生后，我们建议优先生成胎儿/新生儿先天胸腺 具有皮肤归巢特性的淋巴细胞代表着一种发育程序化 将先天淋巴细胞群定位于皮肤以实现“边界”保护的过程 在新生儿阶段，并有助于建立免疫动态平衡。在此应用程序中， 我们建议剖析调控优先收购的分子机制。 胎儿胸腺固有淋巴细胞的皮肤归巢特性及其促进作用 建立皮肤免疫动态平衡。