Langerhans cell
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A Langerhans cell (LC) is a tissue-resident macrophage of the skin<ref>Template:Cite journal</ref> once thought to be a resident dendritic cell.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum.<ref name="Wheaters">Template:Cite book</ref> They also occur in the papillary dermis, particularly around blood vessels,<ref name=Wheaters /> as well as in the mucosa of the mouth, foreskin, and vaginal epithelium.<ref name=pmid7558138 /> They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).
FunctionEdit
In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.<ref name="Monnot">Template:Cite journal</ref>
Generally, tissue-resident macrophages are involved in immune homeostasis and the uptake of apoptotic bodies. However, Langerhans cells can also take on a dendritic cell-like phenotype and migrate to lymph nodes to interact with naive T-cells.Template:Medical citation needed
Matrix metalloproteinase is important and necessary for langerhans cell when it passes stratum basale.<ref>Template:Cite journal</ref>
Langerhans cells derive from primitive erythro-myeloid progenitors that arise in the yolk sac outside the embryo in the first trimester of pregnancy, and under normal circumstances persist throughout life, being replenished by local proliferation as necessary. If the skin becomes severely inflamed, perhaps because of infection, blood monocytes are recruited to the affected region and differentiate into replacement LCs.<ref>Template:Cite journal</ref>
Langerin is a protein found in Langerhans cells,<ref name="pmid14610287">Template:Cite journal</ref> and dendritic cells.<ref name="pmid18086861">Template:Cite journal</ref>
LCs contain a large amount of cannabinoid receptor type 2 (CB2), that by activation by agonists, attenuate both the recruitment of eosinophils and ear swelling in chronic contact dermatitis induced by repeated challenge.<ref>Template:Cite journal</ref>
Clinical significanceEdit
Langerhans cell histiocytosisEdit
In the rare disease Langerhans cell histiocytosis (LCH), an excess of cells similar to these cells are produced. However LCH cells stain positive to CD14 which is a monocyte marker and shows a different, hematopoietic origin for the disorder.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> LCH can cause damage to skin, bone and other organs.Template:Citation needed
HIVEdit
Langerhans cells may be initial cellular targets in the sexual transmission of HIV,<ref>Template:Cite journal</ref> and may be a target, reservoir, and vector of dissemination.<ref>Template:Cite journal</ref> Langerhans cells have been observed in foreskin, vaginal, and oral mucosa of humans; the lower concentrations in oral mucosa suggest that it is not a likely source of HIV infection relative to foreskin and vaginal mucosa.<ref name="pmid7558138">Template:Cite journal</ref>
Human papillomavirusEdit
High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers including cervical, vaginal, anal, and head and neck cancers that cause significant morbidity and mortality worldwide.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Over half of all cervical cancer cases are associated with HPV16, the most common of the cancer-causing high-risk genotypes.<ref>Template:Cite journal</ref> During its natural life cycle, HPV16 infects the basal cells of the epithelium and interacts with Langerhans cells within the epithelial layer,<ref>Template:Cite journal</ref> which are responsible for initiating immune responses against epithelial invading pathogens.<ref>Template:Cite journal</ref> However, HPV does not activate Langerhans cells in vitro, and this may represent a key mechanism by which HPV evades immune detection in vivo.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Specifically, HPV16 entry into Langerhans cells via the annexin A2/S100A10 heterotetramer results in suppressive signaling and lack of Langerhans cell-mediated immune responses.<ref>Template:Cite journal</ref> This Langerhans cell-targeted immune escape mechanism seems to be conserved among different HPV genotypes enabling these viruses to remain undetected in the absence of other inflammatory events.<ref>Template:Cite journal</ref> T cells exposed to these inactivated Langerhans cells are not anergic, and can be activated against HPV upon receiving the appropriate stimuli at a later time point.<ref>Template:Cite journal</ref>
It was demonstrated that Langerhans cells in HPV-induced cervical lesions were spherical, lacked dendrites, and secreted the suppressive cytokine IL-10 in vivo.<ref>Template:Cite journal</ref> The authors further demonstrated that the number of IL-10 secreting immunosuppressive Langerhans cells, and the amount of IL-10 produced in lesions, corresponded with the severity of histopathology and HPV viral load, providing evidence of an active immunosuppressive mechanism employed by HPV that targets Langerhans cells in vivo.Template:Citation needed
Dengue feverEdit
Langerhans cells are also the initial target of the virus that causes dengue fever during its development.<ref>Martina BE, Koraka P, Osterhaus AD (October 2009). "Dengue virus pathogenesis: an integrated view". Clinical Microbiology Reviews. 22 (4): 564–81. doi:10.1128/CMR.00035-09. PMC 2772360. PMID 19822889.</ref>
Declining function during ageingEdit
During ageing the capacity of Langerhans cells to migrate declines.<ref>Template:Cite journal</ref> This compromises immunity and exposes the skin to infectious diseases and cancer.Template:Citation needed
HistoryEdit
Langerhans cells are named after Paul Langerhans, a German physician and anatomist, who discovered the cells at the age of 21 while he was a medical student.<ref>Template:Cite journal</ref> Because of their dendrite-like appearance, he mistakenly identified the cells as part of the nervous system.<ref name="omim-lch">{{#ifeq:|none||{{#switch: | short = OMIM: | shortlink = OMIM: | plain = Online Mendelian Inheritance in Man: | full | #default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if:Langerhans cell histiocytosis |Langerhans cell histiocytosis - }} 604856</ref>