LAUSR

HIGHLIGHTSThe non‐classical MHC pathways are important in skin immunity.CD1 proteins are involved in skin inflammatory diseases.&ggr;&dgr; T cells are key players in skin immunity and tissue homeostasis.Other non‐classical MHC restricted T cells may contribute to skin immunity.Targeting non‐classical T cells has potential in inflammatory skin disease therapy. ABSTRACT The immune network controls homeostasis and inflammation of the skin. Immune cells use their antigen receptors to respond to a wide range of insults originating from microbes and allergens. T cells, which are key effector cells in the immune system, engage their T cell receptors (TCRs) to recognize self and foreign antigens in the context of classical major histocompatibility complex (MHC) molecules, MHC‐like CD1 proteins, or MHC class I‐related molecules. Recently, increasing evidence has demonstrated that T cells activated by non‐canonical antigens are important in skin diseases. This review focuses on recent studies examining the roles of non‐classical antigen‐presenting molecules and their reactive T cells in the skin immune system. Additionally, we describe the types of ligands that activate these unconventional T cells through the non‐classical MHC pathway. Finally, we highlight recent advances in the understanding of the physiological functions of non‐classical T cells in the skin. Further investigation may result in the development of new therapeutic strategies for treating immune‐related skin diseases.