What are Langerhans Cells?
Langerhans cells are specialized dendritic immune cells that reside in the suprabasal layers of the epidermis, functioning as antigen-presenting cells critical for initiating adaptive immune responses and maintaining skin immune surveillance. 1
Anatomical Location and Distribution
- Langerhans cells are dispersed throughout the suprabasal area of the epidermis, forming a contiguous network across the skin surface 1
- They also reside in the basal layers of the epidermis and in the epithelia of the respiratory, digestive, and urogenital tracts 2
- Their strategic positioning at the skin barrier enables them to function as immune sentinels at the interface between the body and external environment 3
Cellular Characteristics and Identification
Immunohistochemical Markers
- Langerhans cells are definitively identified by their expression of S100, CD1a, and Langerin (CD207) 1, 4, 5
- They also express histiocytic markers including CD163 and CD68 1
- These markers distinguish them from other epidermal cell types and are essential for diagnostic confirmation in pathologic conditions 4
Morphology and Structure
- Langerhans cells display a dendritic morphology with processes extending outward to contact adjacent cells 1
- They contain specialized MHC class II-enriched compartments (MIIC) that share characteristics with lysosomes, optimized for antigen processing 6
- The cells possess rough endoplasmic reticulum and Golgi complexes involved in MHC-II molecule biosynthesis 6
Functional Roles in Immunity
Antigen Presentation
- Langerhans cells specialize in acquiring antigens in peripheral tissues, transporting them to regional lymph nodes, and presenting them to naive T cells to initiate adaptive immune responses 2
- They present exogenous antigens in the context of MHC class II molecules to CD4+ T lymphocytes 6
- Freshly isolated Langerhans cells are particularly specialized in endocytosing and processing antigens 6
Dual Immunological Function
- Langerhans cells possess strong immunogenic properties but can also mediate immune tolerance, for example to commensal bacteria 2
- They display functional plasticity, adapting their immunological responses based on microenvironmental cues 7
- At steady state, they maintain an immunoregulatory role, but can shift to proinflammatory or anti-inflammatory effects depending on environmental and endogenous stimuli 8
Specific Immune Processes
- Langerhans cells are involved in antimicrobial immunity and skin immunosurveillance 2
- They play a critical role in the induction phase of contact hypersensitivity 2, 3
- They contribute to the pathogenesis of chronic inflammatory diseases of the skin and mucosa 2
- UVB radiation decreases Langerhans cell numbers, inhibiting their ability to present antigens and altering cytokine secretion 1
Clinical Significance
Langerhans Cell Histiocytosis
- When Langerhans cells undergo neoplastic transformation driven by MAPK/ERK pathway mutations (particularly BRAF V600E in >50% of cases), they cause Langerhans cell histiocytosis 4, 5
- In this disease, the neoplastic cells maintain the characteristic S100+, CD1a+, and Langerin+ phenotype 1, 4, 5
- The lesions show more cellular infiltrates with cytologic atypia compared to reactive Langerhans cells, often with intermixed eosinophils 1
Role in Skin Diseases
- Langerhans cells are involved in inflammatory skin diseases and their regulation is important for disease prevention and treatment 8
- They participate in ultraviolet radiation-induced immunosuppression 3
- Their function impacts tumor immunology, vaccine development, and treatments for inflammatory skin conditions 7
Comparison to Other Epidermal Cells
- Langerhans cells comprise a minority of epidermal cells, while keratinocytes make up 95% of the epidermis 1
- Unlike melanocytes (which produce pigment) and Merkel cells (involved in sensory reception), Langerhans cells are specifically dedicated to immune function 1
- They differ from dermal dendritic cells, though both populations contribute to cutaneous immunity 3