朗格汉斯细胞

朗格汉斯细胞
Langerhans cell
朗格汉斯细胞; Langerhans cell
	皮肤组织的表皮上有大量的朗格汉斯细胞（海洋分枝杆菌感染，S100免疫过氧化物酶染色法（英语：immunoperoxidase））
基本信息
系统	免疫系统
位置	皮肤和黏膜
功能	树状细胞
标识字符
MeSH	D007801
FMA	FMA:63072
	《显微解剖学术语（英语：Anatomical terms of microanatomy）》 [在维基数据上编辑]

朗格汉斯细胞（英语：Langerhans cell，又称兰氏细胞）是在皮肤和黏膜的树状细胞（抗原呈递细胞），其中含有称作伯贝克颗粒（英语：Birbeck granules）的胞器，在上皮中的任何一层都有朗格汉斯细胞，不过主要是在棘状层中^[1]，此类细胞也会出现在血管周围的乳状真皮中^[1]，也会在口腔黏膜（英语：oral mucosa）、包皮及阴道上皮中^[2]。朗格汉斯细胞也会出现在其他组织中，例如若有罹患兰格罕细胞组织球增生症（英语：Langerhans cell histiocytosis），会在淋巴结中发现朗格汉斯细胞。

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功能

皮肤感染时，皮肤的朗格汉斯细胞会吞噬微生物抗原，并且进行处理，会形成抗原呈现细胞（APC）。

一般而言，组织中的树突细胞对于捕捉、吞噬、处理抗原上有高度活性。若树突细胞抵达次级淋巴组织时，可以和新手T细胞（英语：naive T-cell）进行交互作用，但会失去上述有关抗原的活性。

朗格汉斯细胞是在母体怀孕前三个月由卵黄囊中的原始胚胎-骨髓前驱细胞分化而来，一般情况下，各部位的朗格汉斯细胞会持续存在，若有不足，会让该部位的朗格汉斯细胞自行分裂来补充其数量。当皮肤严重发炎（例如感染），血液中的单核球会聚集到发炎位置并分化成朗格汉斯细胞^[3]。朗格汉斯细胞的型态和功能类似巨噬细胞。

兰格汉蛋白（英语：Langerin）（Langerin）是由朗格汉斯细胞^[4]和其他树突细胞所分泌的蛋白质^[5]。

临床重要性

兰格罕细胞组织球增生症

罕见病兰格汉细胞组织球增生症（英语：Langerhans cell histiocytosis）（LCH）会使体内产生许多类似朗格汉斯细胞的细胞。不过LCH细胞对于CD14有呈色反应，而CD14是单核球的标志。这些LCH细胞有着不同的前驱细胞来源，因而造成疾病^[6]。LCH会导致皮肤、骨骼和其他器官损伤。

艾滋病

朗格汉斯细胞可能会成为HIV感染的最初靶细胞^[7]，而且可能成为疾病传播的靶细胞、载体或是媒介^[8]。

在包皮、阴道、或是口腔黏膜中都可观察到朗格汉斯细胞。不过口腔黏膜的朗格汉斯细胞浓度比包皮或阴道都要少。因此人类免疫缺陷病毒可能不是透过口交传播^[2]。

自然-医学杂志在2007年3月刊出了《兰格汉蛋白（英语：Langerin）是朗格汉斯细胞阻止HIV病毒传播的天然屏障》^[9]。此篇文章的作者之一Teunis Geijtenbeek说道：“兰格汉蛋白可以捕捉周遭环境的病毒，因而阻止病毒传播。而因为人体的皮膜附近几乎都有朗格汉斯细胞，因此人类可能与生俱来便有抗病毒的机转，进而摧毁病毒。”^[10]

人类乳突病毒

高风险的人类乳突病毒（HPV）借由性行为传播，并和子宫颈、阴道、头颈部癌症有高度因果关系，全球的发病率以及死亡率都很高^[11]^[12]^[13]^[14]。超过一半的子宫颈癌均和HPV16有关，HPV16是高风险的病毒基因型^[15]。在病毒的生活史中，HPV16感染表皮细胞的基底层，并和表皮下方的朗格汉斯细胞作用^[16]，朗格汉斯细胞的机制是用来防范侵入皮肤的病原体^[17]。不过在实验室中，HPV似乎无法有效活化朗格汉斯细胞，这或许意味着在身体中，HPV也可以躲避免疫系统的辨识与攻击^[18]^[19]^[20]^[21]。

HPV透过annexin A2（英语：annexin A2）/S100A10（英语：S100A10）异质四聚体进入朗格汉斯细胞，并且启动免疫抑制讯号，使朗格汉斯细胞无法有效作用^[22]。这些针对朗格汉斯细胞进行免疫逃避的机制似乎也出现在其他基因型的人类乳突细胞中。这些机制使得病毒无法造成发炎反应，也因此不会被免疫系统发现，也不会被消灭^[23]。不过T细胞面对这些无法受HPV活化的朗格汉斯细胞并非不反应，而是在之后适当的时机点启动对HPV的攻击^[24]。

实验显示，当HPV在子宫颈感染朗格汉斯细胞时，这些细胞会呈现圆球状，而非常见的树突状，并且会分泌抑制性的细胞激素，像是IL-10等等^[25]。研究作者更强调，分泌IL-10免疫抑制性朗格汉斯细胞的数量以及IL-10的分泌量均和组织中的疾病严重度、HPV数量呈正相关。这提供了HPV若感染了朗格汉斯细胞，便会压抑免疫反应的另一个证据。

历史

朗格汉斯细胞得名自发现者保罗·兰格尔翰斯，他是德国医生及解剖学家，在21岁，还在就读医学院时发现这种细胞^[26]。因为这种细胞的形状有树突构造，所以兰格尔翰斯误以为这是神经系统的一部分^[27]。

参见

朗罕氏巨细胞

参考文献

[1]
Young, Barbara; Heath, John W. Wheater's Functional Histology 4th. Churchill Livingstone. 2000: 162. ISBN 0-443-05612-9.
[2]
Hussain, LA; Lehner, T. Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. Immunology. 1995, 85 (3): 475–84. PMC 1383923 . PMID 7558138.
[3]
Collin, Matthew; Milne, Paul. Langerhans cell origin and regulation. Current Opinion in Hematology. 2016, 23 (1): 28–35. PMC 4685746 . doi:10.1097/MOH.0000000000000202.
[4]
Valladeau, Jenny; Dezutter-Dambuyant, Colette; Saeland, Sem. Langerin/CD207 Sheds Light on Formation of Birbeck Granules and Their Possible Function in Langerhans Cells. Immunologic Research. 2003, 28 (2): 93–107. PMID 14610287. doi:10.1385/IR:28:2:93.
[5]
Poulin, Lionel Franz; Henri, Sandrine; de Bovis, Béatrice; Devilard, Elisabeth; Kissenpfennig, Adrien; Malissen, Bernard. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. Journal of Experimental Medicine. 2007, 204 (13): 3119–31. PMC 2150992 . PMID 18086861. doi:10.1084/jem.20071724.
[6]
NCI Summary View > Urology - Yale School of Medicine. medicine.yale.edu. [19 April 2018]. （原始内容存档于2019-06-17）.
[7]
Kawamura, Tatsuyoshi; Kurtz, Stephen E.; Blauvelt, Andrew; Shimada, Shinji. The role of Langerhans cells in the sexual transmission of HIV. Journal of Dermatological Science. 2005, 40 (3): 147–55. PMID 16226431. doi:10.1016/j.jdermsci.2005.08.009.
[8]
Dezutter-Dambuyant, C; Charbonnier, AS; Schmitt, D. 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. December 1995, 43 (10): 882–8. PMID 8786894 （法语）.
[9]
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. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature Medicine. 2007, 13 (3): 367–71. PMID 17334373. doi:10.1038/nm1541.
[10]
Mundell, E. J. Scientists Discover 'Natural Barrier' to HIV. MSN. HealthDay. March 5, 2007 [June 27, 2012]. （原始内容存档于2012-06-09）.
[11]
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. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology. 1999-09-01, 189 (1): 12–19. ISSN 0022-3417. PMID 10451482. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.
[12]
Arbyn, M.; Castellsagué, X.; de Sanjosé, S.; Bruni, L.; Saraiya, M.; Bray, F.; Ferlay, J. Worldwide burden of cervical cancer in 2008. Annals of Oncology. 2011-12-01, 22 (12): 2675–2686. ISSN 1569-8041. PMID 21471563. doi:10.1093/annonc/mdr015.
[13]
Haedicke, Juliane; Iftner, Thomas. Human papillomaviruses and cancer. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2013-09-01, 108 (3): 397–402. ISSN 1879-0887. PMID 23830197. doi:10.1016/j.radonc.2013.06.004.
[14]
HOFFMANN, MARKUS; QUABIUS, ELGAR S.; TRIBIUS, SILKE; HEBEBRAND, LENA; GÖRÖGH, TIBOR; HALEC, GORDANA; KAHN, TOMAS; HEDDERICH, JÜRGEN; RÖCKEN, CHRISTOPH. Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor. Oncology Reports. 2013-05-01, 29 (5): 1962–1968. ISSN 1021-335X. PMC 3658815 . PMID 23467841. doi:10.3892/or.2013.2327.
[15]
Bosch, F. X.; Manos, M. M.; Muñoz, N.; Sherman, M.; Jansen, A. M.; Peto, J.; Schiffman, M. H.; Moreno, V.; Kurman, R. 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. 1995-06-07, 87 (11): 796–802. ISSN 0027-8874. PMID 7791229. doi:10.1093/jnci/87.11.796.
[16]
Stanley, M. A.; Pett, M. R.; Coleman, N. HPV: from infection to cancer. Biochemical Society Transactions. 2007-12-01, 35 (Pt 6): 1456–1460. ISSN 0300-5127. PMID 18031245. doi:10.1042/BST0351456.
[17]
Merad, Miriam; Ginhoux, Florent; Collin, Matthew. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nature Reviews. Immunology. 2008-12-01, 8 (12): 935–947. ISSN 1474-1741. PMID 19029989. doi:10.1038/nri2455.
[18]
Fausch, Steven C.; Da Silva, Diane M.; Rudolf, Michael P.; Kast, W. Martin. Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses. Journal of Immunology. 2002-09-15, 169 (6): 3242–3249. ISSN 0022-1767. PMID 12218143. doi:10.4049/jimmunol.169.6.3242.
[19]
Fausch, Steven C.; Da Silva, Diane M.; Kast, W. Martin. Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells. Cancer Research. 2003-07-01, 63 (13): 3478–3482. ISSN 0008-5472. PMID 12839929.
[20]
Fausch, Steven C.; Fahey, Laura M.; Da Silva, Diane M.; Kast, W. Martin. Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation. Journal of Immunology. 2005-06-01, 174 (11): 7172–7178. ISSN 0022-1767. PMID 15905561. doi:10.4049/jimmunol.174.11.7172.
[21]
Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin. A major role for the minor capsid protein of human papillomavirus type 16 in immune escape. Journal of Immunology. 2009-11-15, 183 (10): 6151–6156. ISSN 1550-6606. PMID 19864613. doi:10.4049/jimmunol.0902145.
[22]
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. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression. Journal of Immunology. 2014-05-15, 192 (10): 4748–4757. ISSN 1550-6606. PMC 4019435 . PMID 24719459. doi:10.4049/jimmunol.1303190.
[23]
Da Silva, Diane M.; Movius, Carly A.; Raff, Adam B.; Brand, Heike E.; Skeate, Joseph G.; Wong, Michael K.; Kast, W. Martin. Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype. Virology. 2014-03-01,. 452-453: 279–286. ISSN 1096-0341. PMC 3987942 . PMID 24606705. doi:10.1016/j.virol.2014.01.031.
[24]
Woodham, Andrew W.; Yan, Lisa; Skeate, Joseph G.; van der Veen, Daniel; Brand, Heike H.; Wong, Michael K.; Da Silva, Diane M.; Kast, W. Martin. T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation. Papillomavirus Research (Amsterdam, Netherlands). December 2016, 2: 21–30. ISSN 2405-8521. PMC 4862606 . PMID 27182559. doi:10.1016/j.pvr.2016.01.002.
[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. Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions. Immunology. 2015-09-01, 146 (1): 113–121. ISSN 1365-2567. PMC 4552506 . PMID 26059395. doi:10.1111/imm.12487.
[26]
Langerhans, Paul. Ueber die Nerven der menschlichen Haut [On the nerves of the human skin]. Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin. 1868, 44 (2–3): 325–37. doi:10.1007/BF01959006 （德语）.
[27]
OMIM Langerhans cell histiocytosis -604856

林大东于益芝，《郎格罕氏细胞分化发育研究进展》《国外医学：免疫学分册》 2000年 23卷 6期
李冰玲　佘锐萍《一种抗原递呈细胞——树突状细胞》《中国兽医杂志》 2000年　26卷　8期　P.53-55

外部链接

[Wheaters-1] [1]
Young, Barbara; Heath, John W. Wheater's Functional Histology 4th. Churchill Livingstone. 2000: 162. ISBN 0-443-05612-9.

[pmid7558138-2] [2]
Hussain, LA; Lehner, T. Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. Immunology. 1995, 85 (3): 475–84. PMC 1383923 . PMID 7558138.

[3] [3]
Collin, Matthew; Milne, Paul. Langerhans cell origin and regulation. Current Opinion in Hematology. 2016, 23 (1): 28–35. PMC 4685746 . doi:10.1097/MOH.0000000000000202.

[pmid14610287-4] [4]
Valladeau, Jenny; Dezutter-Dambuyant, Colette; Saeland, Sem. Langerin/CD207 Sheds Light on Formation of Birbeck Granules and Their Possible Function in Langerhans Cells. Immunologic Research. 2003, 28 (2): 93–107. PMID 14610287. doi:10.1385/IR:28:2:93.

[pmid18086861-5] [5]
Poulin, Lionel Franz; Henri, Sandrine; de Bovis, Béatrice; Devilard, Elisabeth; Kissenpfennig, Adrien; Malissen, Bernard. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. Journal of Experimental Medicine. 2007, 204 (13): 3119–31. PMC 2150992 . PMID 18086861. doi:10.1084/jem.20071724.

[6] [6]
NCI Summary View > Urology - Yale School of Medicine. medicine.yale.edu. [19 April 2018]. （原始内容存档于2019-06-17）.

[7] [7]
Kawamura, Tatsuyoshi; Kurtz, Stephen E.; Blauvelt, Andrew; Shimada, Shinji. The role of Langerhans cells in the sexual transmission of HIV. Journal of Dermatological Science. 2005, 40 (3): 147–55. PMID 16226431. doi:10.1016/j.jdermsci.2005.08.009.

[8] [8]
Dezutter-Dambuyant, C; Charbonnier, AS; Schmitt, D. 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. December 1995, 43 (10): 882–8. PMID 8786894 （法语）.

[9] [9]
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. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature Medicine. 2007, 13 (3): 367–71. PMID 17334373. doi:10.1038/nm1541.

[10] [10]
Mundell, E. J. Scientists Discover 'Natural Barrier' to HIV. MSN. HealthDay. March 5, 2007 [June 27, 2012]. （原始内容存档于2012-06-09）.

[11] [11]
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. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology. 1999-09-01, 189 (1): 12–19. ISSN 0022-3417. PMID 10451482. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.

[12] [12]
Arbyn, M.; Castellsagué, X.; de Sanjosé, S.; Bruni, L.; Saraiya, M.; Bray, F.; Ferlay, J. Worldwide burden of cervical cancer in 2008. Annals of Oncology. 2011-12-01, 22 (12): 2675–2686. ISSN 1569-8041. PMID 21471563. doi:10.1093/annonc/mdr015.

[13] [13]
Haedicke, Juliane; Iftner, Thomas. Human papillomaviruses and cancer. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2013-09-01, 108 (3): 397–402. ISSN 1879-0887. PMID 23830197. doi:10.1016/j.radonc.2013.06.004.

[14] [14]
HOFFMANN, MARKUS; QUABIUS, ELGAR S.; TRIBIUS, SILKE; HEBEBRAND, LENA; GÖRÖGH, TIBOR; HALEC, GORDANA; KAHN, TOMAS; HEDDERICH, JÜRGEN; RÖCKEN, CHRISTOPH. Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor. Oncology Reports. 2013-05-01, 29 (5): 1962–1968. ISSN 1021-335X. PMC 3658815 . PMID 23467841. doi:10.3892/or.2013.2327.

[15] [15]
Bosch, F. X.; Manos, M. M.; Muñoz, N.; Sherman, M.; Jansen, A. M.; Peto, J.; Schiffman, M. H.; Moreno, V.; Kurman, R. 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. 1995-06-07, 87 (11): 796–802. ISSN 0027-8874. PMID 7791229. doi:10.1093/jnci/87.11.796.

[16] [16]
Stanley, M. A.; Pett, M. R.; Coleman, N. HPV: from infection to cancer. Biochemical Society Transactions. 2007-12-01, 35 (Pt 6): 1456–1460. ISSN 0300-5127. PMID 18031245. doi:10.1042/BST0351456.

[17] [17]
Merad, Miriam; Ginhoux, Florent; Collin, Matthew. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nature Reviews. Immunology. 2008-12-01, 8 (12): 935–947. ISSN 1474-1741. PMID 19029989. doi:10.1038/nri2455.

[18] [18]
Fausch, Steven C.; Da Silva, Diane M.; Rudolf, Michael P.; Kast, W. Martin. Human papillomavirus virus-like particles do not activate Langerhans cells: a possible immune escape mechanism used by human papillomaviruses. Journal of Immunology. 2002-09-15, 169 (6): 3242–3249. ISSN 0022-1767. PMID 12218143. doi:10.4049/jimmunol.169.6.3242.

[19] [19]
Fausch, Steven C.; Da Silva, Diane M.; Kast, W. Martin. Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells. Cancer Research. 2003-07-01, 63 (13): 3478–3482. ISSN 0008-5472. PMID 12839929.

[20] [20]
Fausch, Steven C.; Fahey, Laura M.; Da Silva, Diane M.; Kast, W. Martin. Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation. Journal of Immunology. 2005-06-01, 174 (11): 7172–7178. ISSN 0022-1767. PMID 15905561. doi:10.4049/jimmunol.174.11.7172.

[21] [21]
Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin. A major role for the minor capsid protein of human papillomavirus type 16 in immune escape. Journal of Immunology. 2009-11-15, 183 (10): 6151–6156. ISSN 1550-6606. PMID 19864613. doi:10.4049/jimmunol.0902145.

[22] [22]
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. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression. Journal of Immunology. 2014-05-15, 192 (10): 4748–4757. ISSN 1550-6606. PMC 4019435 . PMID 24719459. doi:10.4049/jimmunol.1303190.

[23] [23]
Da Silva, Diane M.; Movius, Carly A.; Raff, Adam B.; Brand, Heike E.; Skeate, Joseph G.; Wong, Michael K.; Kast, W. Martin. Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype. Virology. 2014-03-01,. 452-453: 279–286. ISSN 1096-0341. PMC 3987942 . PMID 24606705. doi:10.1016/j.virol.2014.01.031.

[24] [24]
Woodham, Andrew W.; Yan, Lisa; Skeate, Joseph G.; van der Veen, Daniel; Brand, Heike H.; Wong, Michael K.; Da Silva, Diane M.; Kast, W. Martin. T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation. Papillomavirus Research (Amsterdam, Netherlands). December 2016, 2: 21–30. ISSN 2405-8521. PMC 4862606 . PMID 27182559. doi:10.1016/j.pvr.2016.01.002.

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[omim-lch-27] [27]
OMIM Langerhans cell histiocytosis -604856

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