Differential Regulation and Function of Skin Innate Lymphoid Cells in Homeostasis and Inflammation

Summary Skin is under frequent assaults from environmental agents. Various immune cells reside in the skin to protect against the assaults. Innate lymphoid cells (ILCs) are a family of recently identified innate lymphocytes that are preferentially enriched in barrier tissues such as the skin for local protection but they could be also involved in promoting the skin inflammatory diseases if dysregulated. Understanding how skin-specific localization and function of the innate lymphoid cells are regulated is critical in helping to design the strategy targeting specific innate lymphocyte populations for therapeutic purposes. Our previous study has found that the majority of ILCs in the healthy skin expressed a skin- specific chemokine receptor CCR10. In addition, we found that the skin-specific CCR10+ ILCs were generated in skin-draining lymph nodes (sLNs) under homeostatic conditions with help of skin-associated CD207+ dendritic cells (DCs) and depended on CCR10 for their localization in the skin, where they regulate regulatory and effector T cells to promote skin immune homeostasis. Under immune dysregulatory or inflammatory conditions, generation of CCR10+ ILCs was reduced while there was increased differentiation of CCR10+ ILCs into CCR10- ILCs in the skin, suggesting that CCR10+ and CCR10- ILCs are differentially involved in the skin homeostasis and inflammation. In this application, we will determine cellular and molecular mechanisms underlying generation and function of skin-specific ILCs in homeostasis and inflammation.