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.
Skin is the outmost barrier tissue of a body that is under assaults of different environmental agents right after birth. To protect the skin, immune cells have to be positioned properly in the skin. Many skin diseases such as inflammatory diseases are due to the dysregulated immune homeostasis in the skin. Understanding how the immune system in the skin is established and regulated at the early newborn stage is critical to understand basis of the skin inflammation diseases and other dysfunctions. Findings from our proposed study on regulation of skin-specific migration and localization of innate lymphocytes will aid our understanding of molecular mechanisms regulating the skin immune response, design of better vaccine immunization strategies and development of therapeutic targets in treatment of the skin inflammation diseases.
