The Roles of Skin Langerhans Cells in Immune Tolerance and Cancer Immunity

Abstract

Langerhans cells (LC) are a unique population of tissue-resident macrophages with dendritic cell (DC) functionality that form a network of cells across the epidermis of the skin. Their location at the skin barrier suggests an important role for LC as immune sentinels at the skin surface. The classification of LC as DC over the past few decades has driven the scientific community to extensively study how LC function as DC-like cells that prime T cell immunity. However, LC are a unique type of tissue-resident macrophages, and recent evidence also supports an immunoregulatory role of LC at steady state and during specific inflammatory conditions, highlighting the impact of cutaneous environment in shaping LC functionality. In this mini review, we discuss the recent literature on the immune tolerance function of LC in homeostasis and disease conditions, including malignant transformation and progression; as well as LC functional plasticity for adaption to microenvironmental cues and the potential connection between LC population heterogeneity and functional diversity. Future investigation into the molecular mechanisms that LC use to integrate different microenvironment cues and adapt immunological responses for controlling LC functional plasticity is needed for future breakthroughs in tumor immunology, vaccine development, and treatments for inflammatory skin diseases.

Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus

“…Here, an increase in nitrite production was assessed as a marker for in vitro immunogenicity of the antigen/adjuvant in the particulate form. The nitrite produced by the DCs was quantified using Griess' assay as described previously [37,38]. First, murine DCs were plated at 3 × 10 4 cells/well density.…”

“…The in vitro cytotoxicity of the iCCoV MP and adjuvants MP was tested in DCs using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay as described previously [37,38]. Briefly, DCs were plated in a 96-well plate at the density of 1 × 10 4 cells/well [39].…”

“…Once administered, the vaccine antigen is recognized and engulfed by the circulating APCs via phagocytosis, which is then processed and presented on the surface of these cells via the MHC Class I or MHC class II pathways [34,37,40]. The expression of the antigen-presenting molecules, MHC I/II, and their co-stimulatory molecules, CD80/40, on the surface of DCs was assessed using fluorescent markers through flow cytometry analysis described previously [36][37][38]41]. For this purpose, murine DCs were plated in a 48-well plate at 3 x 10 4 cells/well density.…”

Protective Barriers Provided by the Epidermis

“…Langerhans cells are dendritic, and the dendrites contact nearby keratinocytes. The extension and retraction of the dendrites is a dynamic process called dendrite surveillance extension and retraction cycling [ 115 , 116 ]. This process allows Langerhans cells to survey the environment throughout the viable epidermis and, by penetrating through the tight junctions between granular cells, to reach the stratum corneum [ 110 , 114 , 115 , 116 ].…”

The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells

“…Dendritic cells (DC) are sentinel leukocytes mediating the innate and adaptive immune response in mammalian solid tissue. Dendritic cells play fundamental roles in infections [ 1 , 2 ], inflammation [ 3 ], skin sensitization [ 4 ], and allergy [ 5 ], as well as in cancer [ 6 , 7 , 8 ] and are, therefore, of great interest in research [ 9 ]. The DCs are a heterogenous population of cells, specialized in antigen presenting.…”