Langerhans cell

In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.{{cite journal | vauthors = Monnot GC, Wegrecki M, Cheng TY, Chen YL, Sallee BN, Chakravarthy R, Karantza IM, Tin SY, Khaleel AE, Monga I, Uwakwe LN, Tillman A, Cheng B, Youssef S, Ng SW, Shahine A, Garcia-Vilas JA, Uhlemann AC, Bordone LA, Han A, Rohde CH, Ogg G, Moody DB, Rossjohn J, de Jong A| title = Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a | journal = Nature Immunology | volume = 24 | issue = 1 | pages = 110–122 | date = January 2023 | pmid = 35265979 | doi = 10.1038/s41590-022-01375-z| s2cid = 255039948 | pmc = 10389259 }}

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.{{Medical citation needed|date=June 2021}}

Matrix metalloproteinase is important and necessary for langerhans cell when it passes stratum basale.{{Cite journal |last=Ratzinger |first=Gudrun |last2=Stoitzner |first2=Patrizia |last3=Ebner |first3=Susanne |last4=Lutz |first4=Manfred B. |last5=Layton |first5=Guy T. |last6=Rainer |first6=Christian |last7=Senior |first7=Robert M. |last8=Shipley |first8=J. Michael |last9=Fritsch |first9=Peter |last10=Schuler |first10=Gerold |last11=Romani |first11=Nikolaus |date=2002-05-01 |title=Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin |url=https://pubmed.ncbi.nlm.nih.gov/11970978/ |journal=Journal of Immunology |volume=168 |issue=9 |pages=4361–4371 |doi=10.4049/jimmunol.168.9.4361 |issn=0022-1767 |pmid=11970978}}

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.{{cite journal |doi=10.1097/MOH.0000000000000202 |title=Langerhans cell origin and regulation |year=2016 |last1=Collin|first1=Matthew|last2=Milne|first2=Paul |journal=Current Opinion in Hematology |volume=23 |issue=1 |pages=28–35 |pmc=4685746 |pmid=26554892}}

Langerin is a protein found in Langerhans cells,{{cite journal |doi=10.1385/IR:28:2:93 |title=Langerin/CD207 Sheds Light on Formation of Birbeck Granules and Their Possible Function in Langerhans Cells |year=2003 |last1=Valladeau |first1=Jenny |last2=Dezutter-Dambuyant |first2=Colette |last3=Saeland |first3=Sem |journal=Immunologic Research |volume=28 |issue=2 |pages=93–107 |pmid=14610287|s2cid=37296843 }} and dendritic cells.{{cite journal |doi=10.1084/jem.20071724 |title=The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells |year=2007 |last1=Poulin |first1=Lionel Franz |last2=Henri |first2=Sandrine |last3=de Bovis |first3=Béatrice |last4=Devilard |first4=Elisabeth |last5=Kissenpfennig |first5=Adrien |last6=Malissen |first6=Bernard |journal=Journal of Experimental Medicine |volume=204 |issue=13 |pages=3119–31 |pmid=18086861 |pmc=2150992 |url=http://pure.qub.ac.uk/portal/files/18113605/JEM1_2008.pdf |access-date=2018-11-04 |archive-url=https://web.archive.org/web/20180719214424/https://pure.qub.ac.uk/portal/files/18113605/JEM1_2008.pdf |archive-date=2018-07-19 |url-status=dead }}

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.{{Cite journal |last=Oka |first=Saori |date=2006 |title=Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in Oxazolone-Induced Contact Dermatitis in Mice |url=https://journals.aai.org/jimmunol/article/177/12/8796/74027/Involvement-of-the-Cannabinoid-CB2-Receptor-and |access-date=2023-03-26 |journal=Journal of Immunology |volume=177 |issue=12 |pages=8796–9505 |doi=10.4049/jimmunol.177.12.8796 |pmid=17142782 |s2cid=11946479 |doi-access=free }}

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.{{cite web|url=http://medicine.yale.edu/urology/programs/info.aspx?id=CDR600550|title=NCI Summary View > Urology - Yale School of Medicine|website=medicine.yale.edu|access-date=19 April 2018|archive-url=https://web.archive.org/web/20190617091828/https://medicine.yale.edu/urology/programs/info.aspx?id=CDR600550|archive-date=17 June 2019|url-status=dead}} LCH can cause damage to skin, bone and other organs.{{citation needed|date=June 2023}}

Langerhans cells may be initial cellular targets in the sexual transmission of HIV,{{cite journal |doi=10.1016/j.jdermsci.2005.08.009 |title=The role of Langerhans cells in the sexual transmission of HIV |year=2005 |last1=Kawamura |first1=Tatsuyoshi |last2=Kurtz |first2=Stephen E. |last3=Blauvelt |first3=Andrew |last4=Shimada |first4=Shinji |journal=Journal of Dermatological Science |volume=40 |issue=3 |pages=147–55 |pmid=16226431}} and may be a target, reservoir, and vector of dissemination.{{cite journal |last1=Dezutter-Dambuyant |first1=C |last2=Charbonnier |first2=AS |last3=Schmitt |first3=D |title=Cellules dendritiques épithéliales et infection par HIV-1 in vivo et in vitro |trans-title=Epithelial dendritic cells and HIV-1 infection in vivo and in vitro |language=fr |journal=Pathologie Biologie |volume=43 |issue=10 |pages=882–8 |date=December 1995 |pmid=8786894}} 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.{{cite journal |pmid=7558138 |year=1995 |last1=Hussain |first1=LA |last2=Lehner |first2=T |title=Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia |volume=85 |issue=3 |pages=475–84 |pmc=1383923 |journal=Immunology}}

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.{{Cite journal|title = Human papillomavirus is a necessary cause of invasive cervical cancer worldwide|journal = The Journal of Pathology|date = 1999-09-01|issn = 0022-3417|pmid = 10451482|pages = 12–19|volume = 189|issue = 1|doi = 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F |first1 = J. M.|last1 = Walboomers|first2 = M. V.|last2 = Jacobs|first3 = M. M.|last3 = Manos|first4 = F. X.|last4 = Bosch|first5 = J. A.|last5 = Kummer|first6 = K. V.|last6 = Shah|first7 = P. J.|last7 = Snijders|first8 = J.|last8 = Peto|first9 = C. J.|last9 = Meijer| s2cid=1522249 }}{{Cite journal|title = Worldwide burden of cervical cancer in 2008|journal = Annals of Oncology|date = 2011-12-01|issn = 1569-8041|pmid = 21471563|pages = 2675–2686|volume = 22|issue = 12|doi = 10.1093/annonc/mdr015|first1 = M.|last1 = Arbyn|first2 = X.|last2 = Castellsagué|first3 = S.|last3 = de Sanjosé|first4 = L.|last4 = Bruni|first5 = M.|last5 = Saraiya|first6 = F.|last6 = Bray|first7 = J.|last7 = Ferlay|doi-access = free}}{{Cite journal|title = Human papillomaviruses and cancer|journal = Radiotherapy and Oncology|date = 2013-09-01|issn = 1879-0887|pmid = 23830197|pages = 397–402|volume = 108|issue = 3|doi = 10.1016/j.radonc.2013.06.004|first1 = Juliane|last1 = Haedicke|first2 = Thomas|last2 = Iftner|doi-access = free}}{{Cite journal|title = Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor|journal = Oncology Reports|date = 2013-05-01|issn = 1021-335X|pmc = 3658815|pmid = 23467841|pages = 1962–1968|volume = 29|issue = 5|doi = 10.3892/or.2013.2327|first1 = MARKUS|last1 = HOFFMANN|first2 = ELGAR S.|last2 = QUABIUS|first3 = SILKE|last3 = TRIBIUS|first4 = LENA|last4 = HEBEBRAND|first5 = TIBOR|last5 = GÖRÖGH|first6 = GORDANA|last6 = HALEC|first7 = TOMAS|last7 = KAHN|first8 = JÜRGEN|last8 = HEDDERICH|first9 = CHRISTOPH|last9 = RÖCKEN}} Over half of all cervical cancer cases are associated with HPV16, the most common of the cancer-causing high-risk genotypes.{{Cite journal|title = Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group|journal = Journal of the National Cancer Institute|date = 1995-06-07|issn = 0027-8874|pmid = 7791229|pages = 796–802|volume = 87|issue = 11|first1 = F. X.|last1 = Bosch|first2 = M. M.|last2 = Manos|first3 = N.|last3 = Muñoz|first4 = M.|last4 = Sherman|first5 = A. M.|last5 = Jansen|first6 = J.|last6 = Peto|first7 = M. H.|last7 = Schiffman|first8 = V.|last8 = Moreno|first9 = R.|last9 = Kurman|doi=10.1093/jnci/87.11.796}} During its natural life cycle, HPV16 infects the basal cells of the epithelium and interacts with Langerhans cells within the epithelial layer,{{Cite journal|title = HPV: from infection to cancer|journal = Biochemical Society Transactions|date = 2007-12-01|issn = 0300-5127|pmid = 18031245|pages = 1456–1460|volume = 35|issue = Pt 6|doi = 10.1042/BST0351456|first1 = M. A.|last1 = Stanley|first2 = M. R.|last2 = Pett|first3 = N.|last3 = Coleman}} which are responsible for initiating immune responses against epithelial invading pathogens.{{Cite journal|title = Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells|journal = Nature Reviews. Immunology|date = 2008-12-01|issn = 1474-1741|pmid = 19029989|pages = 935–947|volume = 8|issue = 12|doi = 10.1038/nri2455|first1 = Miriam|last1 = Merad|first2 = Florent|last2 = Ginhoux|first3 = Matthew|last3 = Collin|s2cid = 22286432}} However, HPV does not activate Langerhans cells in vitro, and this may represent a key mechanism by which HPV evades immune detection in vivo.{{Cite journal|title = Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses|journal = Journal of Immunology|date = 2002-09-15|issn = 0022-1767|pmid = 12218143|pages = 3242–3249|volume = 169|issue = 6|first1 = Steven C.|last1 = Fausch|first2 = Diane M.|last2 = Da Silva|first3 = Michael P.|last3 = Rudolf|first4 = W. Martin|last4 = Kast|doi=10.4049/jimmunol.169.6.3242|doi-access = free}}{{Cite journal|title = Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells|journal = Cancer Research|date = 2003-07-01|issn = 0008-5472|pmid = 12839929|pages = 3478–3482|volume = 63|issue = 13|first1 = Steven C.|last1 = Fausch|first2 = Diane M.|last2 = Da Silva|first3 = W. Martin|last3 = Kast}}{{Cite journal|title = Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation|journal = Journal of Immunology|date = 2005-06-01|issn = 0022-1767|pmid = 15905561|pages = 7172–7178|volume = 174|issue = 11|first1 = Steven C.|last1 = Fausch|first2 = Laura M.|last2 = Fahey|first3 = Diane M.|last3 = Da Silva|first4 = W. Martin|last4 = Kast|doi=10.4049/jimmunol.174.11.7172|doi-access = free}}{{Cite journal|title = A major role for the minor capsid protein of human papillomavirus type 16 in immune escape|journal = Journal of Immunology|date = 2009-11-15|issn = 1550-6606|pmid = 19864613|pages = 6151–6156|volume = 183|issue = 10|doi = 10.4049/jimmunol.0902145|first1 = Laura M.|last1 = Fahey|first2 = Adam B.|last2 = Raff|first3 = Diane M.|last3 = Da Silva|first4 = W. Martin|last4 = Kast|pmc = 2947488|doi-access = free}} Specifically, HPV16 entry into Langerhans cells via the annexin A2/S100A10 heterotetramer results in suppressive signaling and lack of Langerhans cell-mediated immune responses.{{Cite journal|title = Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression|journal = Journal of Immunology|date = 2014-05-15|issn = 1550-6606|pmc = 4019435|pmid = 24719459|pages = 4748–4757|volume = 192|issue = 10|doi = 10.4049/jimmunol.1303190|first1 = Andrew W.|last1 = Woodham|first2 = Adam B.|last2 = Raff|first3 = Laura M.|last3 = Raff|first4 = Diane M.|last4 = Da Silva|first5 = Lisa|last5 = Yan|first6 = Joseph G.|last6 = Skeate|first7 = Michael K.|last7 = Wong|first8 = Yvonne G.|last8 = Lin|first9 = W. Martin|last9 = Kast}} 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.{{Cite journal|title = Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a μ genotype|journal = Virology|date = 2014-03-01|issn = 1096-0341|pmc = 3987942|pmid = 24606705|pages = 279–286|volume = 452–453|doi = 10.1016/j.virol.2014.01.031|first1 = Diane M.|last1 = Da Silva|first2 = Carly A.|last2 = Movius|first3 = Adam B.|last3 = Raff|first4 = Heike E.|last4 = Brand|first5 = Joseph G.|last5 = Skeate|first6 = Michael K.|last6 = Wong|first7 = W. Martin|last7 = Kast}} 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.{{Cite journal|last1=Woodham|first1=Andrew W.|last2=Yan|first2=Lisa|last3=Skeate|first3=Joseph G.|last4=van der Veen|first4=Daniel|last5=Brand|first5=Heike H.|last6=Wong|first6=Michael K.|last7=Da Silva|first7=Diane M.|last8=Kast|first8=W. Martin|date=December 2016|title=T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation|journal=Papillomavirus Research (Amsterdam, Netherlands)|volume=2|pages=21–30|doi=10.1016/j.pvr.2016.01.002|issn=2405-8521|pmc=4862606|pmid=27182559}}

It was demonstrated that Langerhans cells in HPV-induced cervical lesions were spherical, lacked dendrites, and secreted the suppressive cytokine IL-10 in vivo.{{Cite journal|title = Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions|journal = Immunology|date = 2015-09-01|issn = 1365-2567|pmc = 4552506|pmid = 26059395|pages = 113–121|volume = 146|issue = 1|doi = 10.1111/imm.12487|first1 = Thiago Theodoro Martins|last1 = Prata|first2 = Camila Mareti|last2 = Bonin|first3 = Alda Maria Teixeira|last3 = Ferreira|first4 = Cacilda Tezelli Junqueira|last4 = Padovani|first5 = Carlos Eurico Dos Santos|last5 = Fernandes|first6 = Ana Paula|last6 = Machado|first7 = Inês Aparecida|last7 = Tozetti}} 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.{{citation needed|date=June 2023}}

Langerhans cells are also the initial target of the virus that causes dengue fever during its development.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.

During ageing the capacity of Langerhans cells to migrate declines.{{Cite journal|title = Lower levels of interleukin-1β gene expression are associated with impaired Langerhans' cell migration in aged human skin |journal = Immunology|volume = 153|issue = 1|pages = 60–70|pmc = 5721243|pmid = 28777886|doi = 10.1111/imm.12810|display-authors=etal|first = S|last = Pilkington|year=2018}} This compromises immunity and exposes the skin to infectious diseases and cancer.{{citation needed|date=June 2023}}

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.{{cite journal |doi=10.1007/BF01959006 |title=Ueber die Nerven der menschlichen Haut |trans-title=On the nerves of the human skin |language=de |year=1868 |last1=Langerhans |first1=Paul |journal=Archiv für pathologische Anatomie und Physiologie und für klinische Medicin |volume=44 |issue=2–3 |pages=325–37|s2cid=6282875 |url=https://zenodo.org/record/2319860 }} Because of their dendrite-like appearance, he mistakenly identified the cells as part of the nervous system.{{OMIM|604856|Langerhans cell histiocytosis}}

• Langhans giant cell
• List of distinct cell types in the adult human body

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• {{eMedicine|derm|216|Langerhans Cell Histiocytosis}}
• {{webarchive |url=https://web.archive.org/web/20040127135809/http://www.trinity.edu/rblyston/MicroA/Lectures/L34-html/img018.jpg |date=January 27, 2004 |title=Illustration at trinity.edu }}
• {{cite journal |first1=Scott C. |last1=Brun |first2=Peter A. D. |last2=Rubin |year=1997 |title=25 year old kickboxer with progressive proptosis |journal=Digital Journal of Ophthalmology |volume=3 |issue=26 |url=http://www.djo.harvard.edu/site.php?url=/physicians/gr/356}}
• {{MeshName|Langerhans+Cells}}

{{Blood}}

Category:Mononuclear phagocytes

Category:Skin anatomy

Category:Epithelial cells