Role of lipid-reactive T cells in skin homeostasis and disease (360G-Wellcome-209222_Z_17_Z)

Immunological mechanisms underlying the maintenance and function of human skin during homeostasis and inflammation remain poorly understood. The majority of our existing knowledge of human cutaneous T cell immunology is based on the study of peptide-specific T cell responses. However, recently it has become clear that T cell responses to lipid-based antigens make major contributions to normal physiology and inflammation in the skin. Specifically, the Major Histocompatibility Complex (MHC) class I-like molecule, CD1a, is highly expressed in human skin. Through collaborative studies, we have recently shown CD1a is able to present lipid antigens to skin T cells, contributing to the inflammatory skin response. The timing is therefore now ideal to address the underlying mechanisms in order to inform new approaches to treatment. In this multinational collaboration, with each principal investigator bringing complementary expertise, reagents and/or cohorts, we aim to investigate the role of lipids in human skin-based immunity. Our interdisciplinary approach will encompass lipidomics, chemistry, clinical dermatology, cellular immunology, and structural biology to identify and characterise the key parameters that define skin-based immunity to lipids. Such information will directly inform disease mechanisms and translational studies aimed at treating inflammatory skin diseases.