Dendritic cell 148367 221426093 2008-06-24T13:11:26Z 72.95.237.49 /* Formation of immature cells */ [[Image:Dendritic cell.JPG|thumb|250px|A dendritic cell]] '''Dendritic cells''' (DCs) are [[immune cell]]s and form part of the [[mammal]]ian [[immune system]]. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as [[antigen-presenting cell]]s. Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the [[skin]] (where a specialized dendritic cell type is called [[Langerhans cell]]s) and the inner lining of the [[nose]], [[lung]]s, [[stomach]] and [[intestine]]s. They can also be found in an immature state in the [[blood]]. Once activated, they migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the ''[[dendrite]]s'', that give the cell its name. However, these do not have any special relation with [[neuron]]s, which also possess similar appendages. Immature dendritic cells are also called '''veiled cells''', in which case they possess large cytoplasmic 'veils' rather than dendrites. ==History== Dendritic cells were first described by Paul Langerhans (Langerhans cells) in the late nineteenth century. It wasn't until 1973, however, that the term "dendritic cells" was coined by [[Ralph M. Steinman]] and [[Zanvil A. Cohn]].<ref name=Steinman>{{cite journal |author=Steinman RM, Cohn ZA |title=Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution |journal=J. Exp. Med. |volume=137 |issue=5 |pages=1142–62 |year=1973 |pmid=4573839|doi=10.1084/jem.137.5.1142}}</ref>. In 2007 Steinman was awarded the [[Albert Lasker Award for Basic Medical Research]] for his discovery. ==Types of dendritic cells== In all dendritic cells, the similar morphology results in a very large contact surface to their surroundings compared to overall cell volume. ===''In vivo'' - primate=== The most common division of dendritic cells is "[[myeloid]]" vs. "[[plasmacytoid]]" (or "[[lymphoid]]"): {| class="wikitable" | '''Name''' || '''Description''' || '''Secretion''' || '''[[Toll-like receptor]]s'''<ref>{{cite journal |author=Sallusto F, Lanzavecchia A |title=The instructive role of dendritic cells on T-cell responses |journal=Arthritis Res. |volume=4 Suppl 3 |issue= |pages=S127–32 |year=2002 |pmid=12110131 |doi=}}</ref> |- | Myeloid dendritic cells (mDC) || are most similar to [[monocyte]]s. mDC are made up of at least two subsets:<BR>(1) the more common mDC-1, which is a major stimulator of T cells<BR>(2) the extremely rare mDC-2, which may have a function in fighting wound infection || [[IL-12]] || [[TLR 2]], [[TLR 4]] |- | Plasmacytoid dendritic cells (pDC) || look like [[plasma cell]]s, but have certain characteristics similar to myeloid dendritic cells.<ref>{{cite journal |author=McKenna K, Beignon A, Bhardwaj N |title=Plasmacytoid dendritic cells: linking innate and adaptive immunity |journal=[[Journal of Virology|J. Virol.]] |volume=79 |issue=1 |pages=17–27 |year=2005 |pmid=15596797 |doi=10.1128/JVI.79.1.17-27.2005}}</ref> || They can produce high amounts of [[interferon|interferon-alpha]] and thus became known as IPC (interferon-producing cells) before their dendritic cell nature was revealed.<ref>{{cite journal |author=Liu YJ |title=IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors |journal=Annu. Rev. Immunol. |volume=23 |issue= |pages=275–306 |year=2005 |pmid=15771572 |doi=10.1146/annurev.immunol.23.021704.115633}}</ref> || [[TLR 7]], [[TLR 9]] |} The markers [[BDCA-2]], [[BDCA-3]], and [[BDCA-4]] can be used to discriminate among the types.<ref>{{cite journal |author=Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck D, Schmitz J |title=BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood |journal=J Immunol |volume=165 |issue=11 |pages=6037–46 |year=2000 |pmid=11086035 |url=http://www.jimmunol.org/cgi/reprint/165/11/6037.pdf }}</ref> Lymphoid and myeloid DCs evolve from lymphoid or myeloid precursors respectively and thus are of [[haematopoietic]] origin. By contrast, [[follicular dendritic cells]] (FDC) are probably not of [[hematopoietic]] origin, but simply look similar to true dendritic cells. ===''In vitro''=== In some respects, dendritic cells cultured [[in vitro]] do not show the same behaviour or capability as dendritic cells isolated ''ex vivo''. Nonetheless, they are often used for research as they are still much more readily available than genuine DCs. * Mo-DC or MDDC refers to cells matured from [[monocyte]]s<ref>{{cite journal |author=Ohgimoto K, Ohgimoto S, Ihara T, Mizuta H, Ishido S, Ayata M, Ogura H, Hotta H |title=Difference in production of infectious wild-type measles and vaccine viruses in monocyte-derived dendritic cells |journal=Virus Res |volume=123 |issue=1 |pages=1–8 |year=2007 |pmid=16959355 |doi=10.1016/j.virusres.2006.07.006}}</ref> * HP-DC refers to cells derived from [[Pluripotential hemopoietic stem cell|hematopoietic progenitor cells]]. ===Nonprimate=== While humans and non-human primates such as [[Rhesus macaque]]s appear to have DCs divided into these groups, other species (such as the [[mouse]]) have different subdivisions of DCs. ==Life cycle== ===Formation of immature cells=== [[Image:Dendritic_Cell_ZP.svg|thumb|Dendritic cell]] Dendritic cells are derived from hemopoietic bone marrow progenitor cells. These progenitor cells initially transform into immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential. Immature dendritic cells constantly sample the surrounding environment for pathogens such as [[virus (biology)|viruses]] and [[bacterium|bacteria]]. This is done through [[pattern recognition receptors]] (PRRs) such as the [[toll-like receptor]]s (TLRs). TLRs recognize specific chemical signatures found on subsets of pathogens. Immature dendritic cells may also phagocytose small quantities of membrane from live own cells, in a process called nibbling. Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and begin to migrate to the [[lymph node]]. Immature dendritic cells phagocytose pathogens and degrade their [[protein]]s into small pieces and upon maturation present those fragments at their cell surface using [[major histocompatibility complex|MHC]] molecules. Simultaneously, they upregulate cell-surface receptors that act as co-receptors in T-cell activation such as [[CD80]] (B7.1), [[CD86]] (B7.2), and [[CD40]] greatly enhancing their ability to activate T-cells. They also upregulate [[chemokine receptor#CCR7|CCR7]], a chemotactic receptor that induces the dendritic cell to travel through the [[blood]] stream to the [[spleen]] or through the [[lymphatic system]] to a [[lymph node]]. Here they act as [[antigen-presenting cell]]s: they activate [[helper T-cell]]s and [[killer T-cell]]s as well as [[B-cell]]s by presenting them with antigens derived from the pathogen, alongside non-antigen specific costimulatory signals. Every helper T-cell is specific to one particular antigen. Only professional [[antigen-presenting cells]] (macrophages, B lymphocytes, and dendritic cells) are able to activate a resting helper T-cell when the matching antigen is presented. However, macrophages and B cells can only activate [[memory T cells]] whereas dendritic cells can activate both memory and [[naive T cells]], and are the most potent of all the antigen-presenting cells. As mentioned above, mDC probably arise from [[monocyte]]s, white blood cells which circulate in the body and, depending on the right signal, can turn into either dendritic cells or [[macrophage]]s. The monocytes in turn are formed from stem cells in the [[bone marrow]]. Monocyte-derived dendritic cells can be generated in vitro from peripheral blood mononuclear cells (PBMCs). Plating of PBMCs in a tissue culture flask permits adherence of monocytes. Treatment of these monocytes with interleukin 4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF) leads to differentiation to immature dendritic cells (iDCs) in about a week. Subsequent treatment with tumor necrosis factor alpha (TNFa) further differentiates the iDCs into mature dendritic cells. ===Life span of dendritic cells=== Activated macrophages have a lifespan of only a few days. The lifespan of activated dendritic cells, while somewhat varying according to type and origin, is of a similar order of magnitude, but immature dendritic cells seem to be able to exist in an inactivated state for much longer. ===Research challenges=== The exact genesis and development of the different types and subsets of dendritic cells and their interrelationship is only marginally understood at the moment, as dendritic cells are so rare and difficult to isolate that only in recent years they have become subject of focused research. Distinct surface antigens that characterize dendritic cells have only become known from 2000 on; before that, researchers had to work with a 'cocktail' of several antigens which, used in combination, result in isolation of cells with characteristics unique to DCs. == Dendritic cells and cytokines == The dendritic cells are constantly in communication with other cells in the body. This communication can take the form of direct cell-to-cell contact based on the interaction of cell-surface proteins. An example of this includes the interaction of the receptor [[CD40]] of the dendritic cell with [[CD40L]] present on the [[lymphocyte]]. However, the cell-cell interaction can also take place at a distance via [[cytokine]]s. For example, stimulating dendritic cells ''in vivo'' with microbial extracts causes the dendritic cells to rapidly begin producing [[IL-12]].<ref name=Reis>{{cite journal |author=Reis e Sousa C, Hieny S, Scharton-Kersten T, Jankovic D, et al |title=In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas |journal=J. Exp. Med. |volume=186 |issue=11 |pages=1819–29 |year=1997 |pmid=9382881 |doi=}}</ref> [[IL-12]] is a signal that helps send naive [[CD4]] T cells towards a [[Th1]] phenotype. The ultimate consequence is priming and activation of the immune system for attack against the antigens which the dendritic cell presents on its surface. However, there are differences in the cytokines produced depending on the type of dendritic cell. The lymphoid DC has the ability to produce huge amounts of [[IFN-a]], more than any other blood cell.<ref name=Siegal>{{cite journal | author=Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, et al | title=The nature of the principal type 1 interferon-producing cells in human blood | journal=Science | date=1999 June 11 | volume=284 | issue=5421 | pages=1835–7 | doi= 10.1126/science.284.5421.1835 | pmid=10364556}}</ref> ==Relationship to HIV, allergy, and autoimmune diseases== [[HIV]], which causes [[AIDS]], can bind to dendritic cells via various receptors expressed on the cell. The best studied example is [[DC-SIGN]] (usually on MDC subset 1, but also on other subsets under certain conditions; since not all dendritic cell subsets express DC-SIGN, its exact role in sexual HIV-1 transmission is not clear). When the dendritic cell takes up HIV and then travels to the lymph node, the virus is able to move to helper T-cells, and this infection of helper T-cells is the major cause of disease. This knowledge has vastly altered our understanding of the infectious cycle of HIV since the mid-1990s, since in the infected dendritic cells, the virus possesses a reservoir which also would have to be targeted by a therapy. This infection of dendritic cells by HIV explains one mechanism by which the virus could persist after prolonged [[HAART]]. Many other viruses, such as the [[SARS]] virus seems to use DC-SIGN to 'hitchhike' to its target cells.<ref>{{cite journal |author=Yang, Zhi-Yong ''et al.'' |title=pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN |journal=[[Journal of Virology|J. Virol.]] |volume=78 |issue=11 |pages=5642–50 |year=2004 |pmid=15140961 |doi=10.1128/JVI.78.11.5642-5650.2004}}</ref> However, most work with virus binding to DC-SIGN expressing cells has been conducted using in vitro derived cells such as moDCs. The physiological role of DC-SIGN in vivo is more difficult to ascertain. Altered function of dendritic cells is also known to play a major or even key role in [[allergy]] and [[autoimmune disease]]s like [[lupus erythematosus]]. ==Dendritic cells in animals other than humans== The above applies to humans. In other organisms, the function of dendritic cells can differ slightly. For example, in [[brown rat]]s (but not mice), a subset of dendritic cells exists that displays pronounced killer cell-like activity, apparently through its entire lifespan{{Fact|date=February 2007}}. However, the principal function of dendritic cells as known to date is always to act as an immune sentinel. They survey the body and collect information relevant to the immune system, they are then able to instruct and direct the adaptive arms to respond to challenges. In addition, an immediate precursor to myeloid and lymphoid dendritic cells of the spleen has been identified.<ref name=Naik>{{cite journal | author=Naik SH, Metcalf D, van Nieuwenhuijze A, et al. | journal=Nature Immunolgy | title=Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes | date=2006 Jun | volume=7 | issue=6 | pages=663–71 | doi=10.1038/ni1340}}</ref> This precursor, termed pre-DC, lacks MHC class II surface expression, and is distinct from monocytes, which primarily give rise to DCs in non-lymphoid tissues. ==Media== {{multi-video start}} {{multi-video item|filename=S8-Dendritic Cells Dragging Conidia in Collagen.ogg|title=Dendritic Cells interacting with conidia in collagen|description=A well resolved dendritic cell drags a [[conidium]]<br> through a distance of up to 9 μm. The conidium, however, is not [[phagocytosis|phagocytosed]] by the cell.<br> The observation was made over 3 h with one frame every 30 s.|format=[[Theora]]}} {{multi-video item|filename=S6-Dendritic Cells with Conidia in Collagen.ogg|title=Phagocytosis by dendritic cells|description=A single dendritic cell can be seen here efficiently taking up at least four conidia in its vicinity.|format=[[Theora]]}} {{multi-video end}} ==See also== *[[List of human clusters of differentiation]] for a list of CD molecules (as [[CD80]] and [[CD86]]) == External links == *{{MeshName|Dendritic+Cells}} *[http://www.healthsystem.virginia.edu/internet/hematology/HessEDD/BenignHematologicDisorders/normal-hematopoietic-cells/Dendritic-cell.cfm Dendritic cells] Presented by the University of Virginia *[http://www.dc2007.eu www.dc2007.eu : 5<sup>th</sup> International Meeting on Dendritic Cell Vaccination and other Strategies to tip the Balance of the Immune System] *[http://www.rockefeller.edu/labheads/steinman/steinman-lab.php Website of Dr. Ralph M. Steinman at The Rockefeller University] contains information on DCs, links to articles, pictures and videos == References == {{Reflist|2}} {{Blood}} [[Category:Mononuclear phagocytes]] [[Category:Human cells]] [[de:Dendritische Zelle]] [[es:Célula dendrítica]] [[fr:Cellule dendritique]] [[ko:수지상 세포]] [[id:Sel dendritik]] [[he:תא דנדריטי]] [[nl:Dendritische cel]] [[ja:樹状細胞]] [[pl:Komórka dendrytyczna]] [[pt:Célula dendrítica]] [[ru:Дендритные клетки]] [[vi:Tế bào tua]] [[ur:شجری خلیہ]] [[zh:樹狀細胞]]