The representation of Langerhans cells in the Cell Ontology. A portion of the Cell Ontology is shown with ovals corresponding to cell types defined in the ontology and arrows corresponding to relations between those cell types. Langerhans cell is represented by a yellow oval; blue arrows correspond to is_a relations, and orange arrows correspond to develops_from relations. Only a subset of Langerhans cell parent types are included in the figure.[1]
Langerhans cells derive from primitive erythro-myeloid progenitors that arise in the yolk sac outside theembryo in the first trimester of pregnancy, and under normal circumstances persist throughout life, being replenished by localproliferation as necessary. If the skin becomes severely inflamed, perhaps because of infection, blood monocytes are recruited to the affected region anddifferentiate into replacement LCs.[8]
In therare diseaseLangerhans cell histiocytosis (LCH), an excess of cells similar to these cells are produced. However LCH cells stain positive toCD14 which is a monocyte marker and shows a different, hematopoietic origin for the disorder.[12] LCH can cause damage toskin,bone and other organs.[citation needed]
Langerhans cells may be initial cellular targets in the sexual transmission of HIV,[13] and may be a target, reservoir, and vector of dissemination.[14] 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 ofHIV infection relative to foreskin and vaginal mucosa.[5]
High-riskhuman 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.[15][16][17][18] Over half of allcervical cancer cases are associated with HPV16, the most common of the cancer-causing high-risk genotypes.[19] During its natural life cycle, HPV16 infects the basal cells of the epithelium and interacts with Langerhans cells within the epithelial layer,[20] which are responsible for initiating immune responses against epithelial invading pathogens.[21] However, HPV does not activate Langerhans cellsin vitro, and this may represent a key mechanism by which HPV evades immune detectionin vivo.[22][23][24][25] Specifically, HPV16 entry into Langerhans cells via theannexin A2/S100A10 heterotetramer results in suppressive signaling and lack of Langerhans cell-mediated immune responses.[26] 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.[27] 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.[28]
It was demonstrated that Langerhans cells in HPV-induced cervical lesions were spherical, lacked dendrites, and secreted the suppressive cytokine IL-10in vivo.[29] The authors further demonstrated that the number ofIL-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 cellsin vivo.[citation needed]
During ageing the capacity of Langerhans cells to migrate declines.[31] This compromises immunity and exposes the skin to infectious diseases and cancer.[citation needed]
^Valladeau, Jenny; Dezutter-Dambuyant, Colette; Saeland, Sem (2003). "Langerin/CD207 Sheds Light on Formation of Birbeck Granules and Their Possible Function in Langerhans Cells".Immunologic Research.28 (2):93–107.doi:10.1385/IR:28:2:93.PMID14610287.S2CID37296843.
^Kawamura, Tatsuyoshi; Kurtz, Stephen E.; Blauvelt, Andrew; Shimada, Shinji (2005). "The role of Langerhans cells in the sexual transmission of HIV".Journal of Dermatological Science.40 (3):147–55.doi:10.1016/j.jdermsci.2005.08.009.PMID16226431.
^Dezutter-Dambuyant, C; Charbonnier, AS; Schmitt, D (December 1995). "Cellules dendritiques épithéliales et infection par HIV-1 in vivo et in vitro" [Epithelial dendritic cells and HIV-1 infection in vivo and in vitro].Pathologie Biologie (in French).43 (10):882–8.PMID8786894.
^Bosch, F. X.; Manos, M. M.; Muñoz, N.; Sherman, M.; Jansen, A. M.; Peto, J.; Schiffman, M. H.; Moreno, V.; Kurman, R. (1995-06-07). "Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group".Journal of the National Cancer Institute.87 (11):796–802.doi:10.1093/jnci/87.11.796.ISSN0027-8874.PMID7791229.
^Stanley, M. A.; Pett, M. R.; Coleman, N. (2007-12-01). "HPV: from infection to cancer".Biochemical Society Transactions.35 (Pt 6):1456–1460.doi:10.1042/BST0351456.ISSN0300-5127.PMID18031245.
^Merad, Miriam; Ginhoux, Florent; Collin, Matthew (2008-12-01). "Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells".Nature Reviews. Immunology.8 (12):935–947.doi:10.1038/nri2455.ISSN1474-1741.PMID19029989.S2CID22286432.
^Fausch, Steven C.; Da Silva, Diane M.; Kast, W. Martin (2003-07-01). "Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells".Cancer Research.63 (13):3478–3482.ISSN0008-5472.PMID12839929.
