Langerhans cell

Like other dendritic cells, the Langerhans cell, together with monocytes, macrophages and B lymphocytes, belongs to the so-called "professional" antigen-presenting cells of the immune system. It occupies a key position in the innate and adaptive immune system.

Between the epithelial cells of the skin and the adjacent mucous membranes lie the somewhat lighter Langerhans cells. They make up about 4.5% of the cell population in the epidermis. Langerhans cells originate in the bone marrow and migrate from there into epidermis and other surface epithelia. Although hematopoietic in origin, they lack the typical markers of other leukocytes such as CD3, CD20, CD14, CD15, CD56. In the epidermis, Langerhans cells are anchored to surrounding keratinocytes via E-cadherin. Langerhans cells are comparable to the so-called M cells which are localized in the surface epithelium of Peyer`s plaques and represent a part of the MALT system.

Morphologically, the cells are characterized by a lobulated nucleus. They possess long, deer antler-like branched (dendritic) projections without desmosomes. Their > 10 µm long dendrites spread in a reticular fashion along the intercellular spaces through the so-called tight junctions of the epithelia. In the epidermis, the dendritic extensions extend below the stratum corneum. These extensions (dendrites) are in constant motion. They are retracted and pushed forward again at another location. In this process, the sealing function of the covering epithelia of the inner and outer surfaces (diffusion barrier) is not impaired. However, due to the mobility of their dendrites, Langerhans cells are able to intercept invading pathogens and antigens at an early stage (sentry of the immune system) in order to prepare them for a specific immunological response. Langerhans cells have a lifespan of up to 4 months.

Langerhans cells can only be reliably identified under the light microscope by special immunological staining. Antigens that only express Langerhans cells and not keratinocytes include: Langerin, CD1a, the low-affinity Fc-gamma receptor II (CD32), the high-affinity Fc-epsilon receptor I and the class II antigens encoded by the MHC gene (HLA-DR, HALA-DQ, HLA-DP). The protein S100 stains melanocytes and Langerhans cells simultaneously, but gives a good picture of the filigree network of both cell systems.

Electron microscopy can be used to detect the characteristic tennis racket-like, trilamellar Birbeck granules of Langerhans cells. These granules contain the C-type lectin Langerin (CD207). Via Langerin, Langerhans cells can introduce lipid antigens into the CD1 presentation pathway.

Langerhans cells phagocytise foreign material, process it and present it to the T-lymphocytes on their surface after complexation with MHC II, MHC I and/or CD1a. Further co-factors(cytokines) define the quantity and quality of the initiated immune response in this recognition and presentation process. Langerhans cells increasingly express Langerin (see also CD1a+Langerin+ dendritic cells).

After antigen uptake, Langerhans cells migrate from the surface epithelia (e.g. from the epidermis) and settle in nearby lymph nodes. During this migration, the morphology of the Langerhans cell changes: the long dendrites are now replaced by veil-like membrane folds. These now morphologically completely changed cells were originally also called "veil(ed) cells". Veiled cells migrate via the afferent lymphatic pathways into the regional lymph nodes. Here they present as interdigitating dendritic cells the absorbed antigens for T-lymphocytes to activate them.

If the surface epithelia are structurally damaged by external influences, the morphological picture of the Langernhans cell changes. Size and dendricity increase. The adhesion of Langerhans cells to the surrounding keratinocytes is resolved by the downregulation of the E-cadherin molecule by the interleukins -1 alpha and -1beta as well as TNF-alpha. At the same time, their immunophenotype shifts from antigen uptake status to immune stimulation mode (Schuler G. et al. 1985).

When a larger contingent of Langerhans cells is destroyed (e.g. by inflammation or mechanically), their repopulation occurs by immigration of classical monocytes of peripheral blood into the surface epithelium. In a second wave, replacements are made from myeloid precursors. This ensures a stable self-renewal of the Langerhans cell network (Collin M et al. 2016). This is an eminently important prerequisite for the immunological homeostasis of the surfaces and thus the immunological integrity of the entire organism.

Apparently, the loss of Langerhans cells of the skin plays an essential role in the congenital zinc deficiency syndrome (see below Acrodermatitis enteropathica).

1. Brüggen MC et al. (2016) Antigen or allergen presentation. In: Allergology, Biedermann T et al. (Hrsg) Springer-Verlag S 56 -57
2. Collin M et al (2016) Langerhans cell origin and regulation. Curr Opin Hematol 23: 28-35.
3. Schuler G. et al (1985) Murine epidermal Langerhans cells matur into potent immunostimulatory dendritic cells in vitro. J Exp Med 161: 526-546