Langerhans cell

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Not to be confused with the cells of the islets of Langerhans, found in the pancreas, or Langhans giant cell.
Section of skin showing large numbers of dendritic cells (Langerhans cells) in the epidermis. (M. ulcerans infection, S100 immunoperoxidase stain.)
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 are dendritic cells (antigen-presenting immune cells) of the skin and mucosa, and contain large organelles called Birbeck granules. They are present in all layers of the epidermis, but are most prominent in the stratum spinosum.[2] They also occur in the papillary dermis, particularly around blood vessels,[2] as well as in the mucosa of the mouth, foreskin, and vagina.[3] They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).


In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.

Generally, dendritic cells in tissue are active in the capture, uptake and processing of antigens. Once dendritic cells arrive in secondary lymphoid tissue, however, they lose these properties while gaining the capacity to interact with naive T-cells.

Langerhans cells derive from the cellular differentiation of monocytes with the marker "Gr-1" (also known as "Ly-6G"). This differentiation requires stimulation by colony stimulating factor (CSF)-1.[4] They are similar in morphology and function to macrophages.

Langerin is a protein found in Langerhans cells,[5] and other types of dendritic cells.[6]

Clinical significance[edit]


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.[7] LCH can cause damage to skin, bone and other organs.


Langerhans cells may be initial cellular targets in the sexual transmission of HIV,[8] and may be a target, reservoir, and vector of dissemination.[9]

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.[3]

On March 4, 2007 the online Nature Medicine magazine published the research letter "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells."[10] One of the authors of the study, Teunis Geijtenbeek, said that "Langerin is able to scavenge viruses from the surrounding environment, thereby preventing infection" and "since generally all tissues on the outside of our bodies have Langerhans cells, we think that the human body is equipped with an antiviral defense mechanism, destroying incoming viruses."[11]


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.[12][13][14][15] Over half of all cervical cancer cases are associated with HPV16, the most common of the cancer-causing high-risk genotypes.[16] During its natural life cycle, HPV16 infects the basal cells of the epithelium and interacts with Langerhans cells within the epithelial layer,[17] which are responsible for initiating immune responses against epithelial invading pathogens.[18] However, HPV does not activate Langerhans cells in vitro, and this may represent a key mechanism by which HPV evades immune detection in vivo.[19][20][21][22] Specifically, HPV16 entry into Langerhans cells via the annexin A2/S100A10 heterotetramer results in suppressive signaling and lack of Langerhans cell-mediated immune responses.[23] 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.[24]

It was demonstrated that Langerhans cells in HPV-induced cervical lesions were spherical, lacked dendrites, and secreted the suppressive cytokine IL-10 in vivo.[25] 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.


The Langerhans cell is named after Paul Langerhans, a German physician and anatomist, who discovered the cells at the age of 21 while he was a medical student.[26] Because of their dendritic nature, he mistakenly identified the cells as part of the nervous system.[27]

See also[edit]


  1. ^ Masci, Anna; Arighi, Cecilia N; Diehl, Alexander D; Lieberman, Anne E; Mungall, Chris; Scheuermann, Richard H; Smith, Barry; Cowell, Lindsay G (2009). "An improved ontological representation of dendritic cells as a paradigm for all cell types". BMC Bioinformatics 10: 70. doi:10.1186/1471-2105-10-70. PMC 2662812. PMID 19243617. 
  2. ^ a b Young, Barbara; Heath, John W. (2000). Wheater's Functional Histology (4th ed.). Churchill Livingstone. p. 162. ISBN 0-443-05612-9. 
  3. ^ a b Hussain, LA; Lehner, T (1995). "Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia". Immunology 85 (3): 475–84. PMC 1383923. PMID 7558138. 
  4. ^ Ginhoux, Florent; Tacke, Frank; Angeli, Veronique; Bogunovic, Milena; Loubeau, Martine; Dai, Xu-Ming; Stanley, E Richard; Randolph, Gwendalyn J; Merad, Miriam (2006). "Langerhans cells arise from monocytes in vivo". Nature Immunology 7 (3): 265–73. doi:10.1038/ni1307. PMID 16444257. 
  5. ^ 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. PMID 14610287. 
  6. ^ Poulin, Lionel Franz; Henri, Sandrine; de Bovis, Béatrice; Devilard, Elisabeth; Kissenpfennig, Adrien; Malissen, Bernard (2007). "The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells". Journal of Experimental Medicine 204 (13): 3119–31. doi:10.1084/jem.20071724. PMC 2150992. PMID 18086861. 
  7. ^
  8. ^ 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. PMID 16226431. 
  9. ^ 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. PMID 8786894. 
  10. ^ De Witte, Lot; Nabatov, Alexey; Pion, Marjorie; Fluitsma, Donna; De Jong, Marein A W P; De Gruijl, Tanja; Piguet, Vincent; Van Kooyk, Yvette; Geijtenbeek, Teunis B H (2007). "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells". Nature Medicine 13 (3): 367–71. doi:10.1038/nm1541. PMID 17334373. 
  11. ^ Mundell, E. J. (March 5, 2007). "Scientists Discover 'Natural Barrier' to HIV". MSN. HealthDay. Retrieved June 27, 2012. 
  12. ^ Walboomers, J. M.; Jacobs, M. V.; Manos, M. M.; Bosch, F. X.; Kummer, J. A.; Shah, K. V.; Snijders, P. J.; Peto, J.; Meijer, C. J. (1999-09-01). "Human papillomavirus is a necessary cause of invasive cervical cancer worldwide". The Journal of Pathology 189 (1): 12–19. doi:10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F. ISSN 0022-3417. PMID 10451482. 
  13. ^ Arbyn, M.; Castellsagué, X.; de Sanjosé, S.; Bruni, L.; Saraiya, M.; Bray, F.; Ferlay, J. (2011-12-01). "Worldwide burden of cervical cancer in 2008". Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 22 (12): 2675–2686. doi:10.1093/annonc/mdr015. ISSN 1569-8041. PMID 21471563. 
  14. ^ Haedicke, Juliane; Iftner, Thomas (2013-09-01). "Human papillomaviruses and cancer". Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology 108 (3): 397–402. doi:10.1016/j.radonc.2013.06.004. ISSN 1879-0887. PMID 23830197. 
  15. ^ HOFFMANN, MARKUS; QUABIUS, ELGAR S.; TRIBIUS, SILKE; HEBEBRAND, LENA; GÖRÖGH, TIBOR; HALEC, GORDANA; KAHN, TOMAS; HEDDERICH, JÜRGEN; RÖCKEN, CHRISTOPH (2013-05-01). "Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor". Oncology Reports 29 (5): 1962–1968. doi:10.3892/or.2013.2327. ISSN 1021-335X. PMC 3658815. PMID 23467841. 
  16. ^ 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. ISSN 0027-8874. PMID 7791229. 
  17. ^ 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. ISSN 0300-5127. PMID 18031245. 
  18. ^ 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. ISSN 1474-1741. PMID 19029989. 
  19. ^ Fausch, Steven C.; Da Silva, Diane M.; Rudolf, Michael P.; Kast, W. Martin (2002-09-15). "Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses". Journal of Immunology (Baltimore, Md.: 1950) 169 (6): 3242–3249. ISSN 0022-1767. PMID 12218143. 
  20. ^ 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. ISSN 0008-5472. PMID 12839929. 
  21. ^ Fausch, Steven C.; Fahey, Laura M.; Da Silva, Diane M.; Kast, W. Martin (2005-06-01). "Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation". Journal of Immunology (Baltimore, Md.: 1950) 174 (11): 7172–7178. ISSN 0022-1767. PMID 15905561. 
  22. ^ Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin (2009-11-15). "A major role for the minor capsid protein of human papillomavirus type 16 in immune escape". Journal of Immunology (Baltimore, Md.: 1950) 183 (10): 6151–6156. doi:10.4049/jimmunol.0902145. ISSN 1550-6606. PMID 19864613. 
  23. ^ Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin (2014-05-15). "Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression". Journal of Immunology (Baltimore, Md.: 1950) 192 (10): 4748–4757. doi:10.4049/jimmunol.1303190. ISSN 1550-6606. PMC 4019435. PMID 24719459. 
  24. ^ Da Silva, Diane M.; Movius, Carly A.; Raff, Adam B.; Brand, Heike E.; Skeate, Joseph G.; Wong, Michael K.; Kast, W. Martin (2014-03-01). "Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype". Virology. 452-453: 279–286. doi:10.1016/j.virol.2014.01.031. ISSN 1096-0341. PMC 3987942. PMID 24606705. 
  25. ^ Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico Dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida (2015-09-01). "Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions". Immunology 146 (1): 113–121. doi:10.1111/imm.12487. ISSN 1365-2567. PMC 4552506. PMID 26059395. 
  26. ^ Langerhans, Paul (1868). "Ueber die Nerven der menschlichen Haut" [On the nerves of the human skin]. Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (in German) 44 (2–3): 325–37. doi:10.1007/BF01959006. 
  27. ^ Online 'Mendelian Inheritance in Man' (OMIM) Langerhans cell histiocytosis -604856

External links[edit]