Myeloid C-type lectin receptors in skin/mucoepithelial diseases and tumors

Abstract Myeloid C-type lectin receptors (CLRs), which consist of an extracellular carbohydrate recognition domain and intracellular signal transducing motif such as the immunoreceptor tyrosine-based activation motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM), are innate immune receptors primarily expressed on myeloid lineage cells such as dendritic cells (DCs) and Mϕs. CLRs play important roles in host defense against infection by fungi and bacteria by recognizing specific carbohydrate components of these pathogens. However, these immune receptors also make important contributions to immune homeostasis of mucosa and skin in mammals by recognizing components of microbiota, as well as by recognizing self-components such as alarmins from dead cells and noncanonical non-carbohydrate ligands. CLR deficiency not only induces hypersensitivity to infection, but also causes dysregulation of muco-cutaneous immune homeostasis, resulting in the development of allergy, inflammation, autoimmunity, and tumors. In this review, we introduce recent discoveries regarding the roles of myeloid CLRs in the immune system exposed to the environment, and discuss the roles of these lectin receptors in the development of colitis, asthma, psoriasis, atopic dermatitis, and cancer. Although some CLRs are suggested to be involved in the development of these diseases, the function of CLRs and their ligands still largely remain to be elucidated.