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

总结 皮肤是身体最外层的上皮组织，经常受到 环境代理人。保护自己不受攻击并维持局部组织 为了保持皮肤的完整性，免疫细胞需要正确地定位在皮肤中。一组免疫 细胞，即先天淋巴样细胞（ILC），优先定位于皮肤中， 它们起到第一道防线的作用，但也可能导致皮肤炎症， 例如局部皮炎和牛皮癣的疾病。这个目标 该项目的目的是了解皮肤中ILC的建立是如何调节的， 在早期胎儿/新生儿阶段的免疫保护和皮肤的稳态。我们 初步研究发现了一种新的过程，指导胎儿/新生儿胸腺NK 1.1 + ILC获得皮肤归巢属性，用于其特定定位到皮肤中。 考虑到皮肤是下攻击的环境代理人后立即 出生时，我们提出，胎儿/新生儿先天胸腺的优先代 具有皮肤归巢特性的淋巴细胞代表了一种发育程序， 将先天淋巴细胞群体靶向皮肤以进行“边界”保护的过程 并帮助建立免疫稳态。在本申请中， 我们建议剖析调节优先获得的分子机制， 胎儿胸腺固有淋巴细胞皮肤归巢特性及其在促进 皮肤免疫稳态的建立。

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.