Role of non-classical T cells in skin immunity

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.