PREFERENTIAL PERINATAL THYMIC PROGRAMMING OF SKIN-HOMING INNATE LYMPHOID CELLS IN EARLY ESTABLISHMENT OF SKIN HOMEOSTASIS

The skin is the outmost epithelial tissue of a body that is under frequent assaults ofenvironmental agents. To protect against the assaults and maintain the local tissueintegrity, immune cells need to be properly positioned in the skin. A group of immunecells, namely innate lymphoid cells (ILCs), are preferentially localized in the skin wherethey function as the first line of defense but can also contribute to the skin inflammatorydiseases such as topical dermatitis and psoriasis when dysregulated. The goal of thisproject is to understand how the establishment of ILCs in the skin is regulated for theimmune protection and homeostasis of the skin during early fetal/neonatal stages. Ourpreliminary 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 afterthe birth, we propose that the preferential generation of fetal/neonatal thymic innatelymphocytes with skin-homing properties represents a developmentally programmedprocess that targets innate lymphocyte populations to the skin for the ?border? protectionin the neonatal stage and helps establish the immune homeostasis. In this application,we propose to dissect molecular mechanisms regulating the preferential acquisition ofthe skin-homing property by fetal thymic innate lymphocytes and its roles in promotingthe establishment of skin immune homeostasis.