Editing Dendritic cell (section)

== Disease ==

=== Blastic plasmacytoid dendritic cell neoplasm ===
Blastic plasmacytoid dendritic cell neoplasm is a rare type of [[myeloid]] cancer in which malignant pDCs infiltrate the skin, bone marrow, central nervous system, and other tissues. Typically, the disease presents with skin lesions (e.g. nodules, tumors, [[papule]]s, bruise-like patches, and/or ulcers) that most often occur on the head, face, and upper torso.<ref name="pmid29760611">{{cite journal | vauthors = Owczarczyk-Saczonek A, Sokołowska-Wojdyło M, Olszewska B, Malek M, Znajewska-Pander A, Kowalczyk A, Biernat W, Poniatowska-Broniek G, Knopińska-Posłuszny W, Kozielec Z, Nowicki R, Placek W | title = Clinicopathologic retrospective analysis of blastic plasmacytoid dendritic cell neoplasms | journal = Postepy Dermatologii I Alergologii | volume = 35 | issue = 2 | pages = 128–138 | date = April 2018 | pmid = 29760611 | pmc = 5949541 | doi = 10.5114/ada.2017.72269 }}</ref> This presentation may be accompanied by cPC infiltrations into other tissues to result in swollen [[lymph node]]s, enlarged liver, enlarged spleen, symptoms of [[central nervous system]] dysfunction, and similar abnormalities in breasts, eyes, kidneys, lungs, gastrointestinal tract, bone, sinuses, ears, and/or testes.<ref name="pmid28906324"/> The disease may also present as a pDC [[leukemia]], i.e. increased levels of malignant pDC in blood (i.e. >2% of nucleated cells) and bone marrow and evidence (i.e. [[cytopenia]]s) of [[bone marrow failure]].<ref name="pmid28906324">{{cite journal | vauthors = Kim MJ, Nasr A, Kabir B, de Nanassy J, Tang K, Menzies-Toman D, Johnston D, El Demellawy D | title = Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review | journal = Journal of Pediatric Hematology/Oncology | volume = 39 | issue = 7 | pages = 528–537 | date = October 2017 | pmid = 28906324 | doi = 10.1097/MPH.0000000000000964 | s2cid = 11799428 }}</ref> Blastic plasmacytoid dendritic cell neoplasm has a high rate of recurrence following initial treatments with various [[chemotherapy]] regimens. In consequence, the disease has a poor overall prognosis and newer [[Blastic plasmacytoid dendritic cell neoplasm#Treatment|chemotherapeutic]] and novel [[Blastic plasmacytoid dendritic cell neoplasm#Novel treatments|non-chemotherapeutic drug]] regimens to improve the situation are under study.<ref name="pmid29455234">{{cite journal | vauthors = Wang S, Wang X, Liu M, Bai O | title = Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel agents | journal = Annals of Hematology | volume = 97 | issue = 4 | pages = 563–572 | date = April 2018 | pmid = 29455234 | doi = 10.1007/s00277-018-3259-z | s2cid = 3627886 }}</ref>

=== Viral infection ===
[[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){{Citation needed|date=February 2011}}. When the dendritic cell takes up HIV and then travels to the lymph node, the virus can be transferred to helper CD4+ T-cells,<ref>{{cite journal |vauthors=Cavrois M, Neidleman J, Kreisberg JF, Greene WC |title=In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions  |journal=PLOS Pathogens |volume=3 |issue=1 |pages=e4 |year=2007 |doi=10.1371/journal.ppat.0030004 |pmid=17238285 |pmc=1779297 |doi-access=free }}</ref> contributing to the developing infection. This infection of dendritic cells by HIV explains one mechanism by which the virus could persist after prolonged [[Antiretroviral drug|HAART]].{{Citation needed|date=February 2011}}

Many other viruses, such as the [[SARS]] virus, seem to use DC-SIGN to 'hitchhike' to its target cells.<ref>{{cite journal |author=Yang, Zhi-Yong|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 |pmc=415834|display-authors=etal}}</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.

=== Cancer ===
Dendritic cells are usually not abundant at tumor sites, but increased densities of populations of dendritic cells have been associated with better clinical outcome, suggesting that these cells can participate in controlling cancer progression.<ref name="pmid25446897">{{cite journal | vauthors = Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF | title = Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity | journal = Cancer Cell | volume = 10 | issue = 26 | pages = 638–52 | date = November 2014 | pmid = 25446897 | doi = 10.1016/j.ccell.2014.09.007 | pmc=4254577 }}</ref><ref name="pmid30955881">{{cite journal | vauthors = Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, Tsui J, Ruhland MK, Kersten K, Abushawish MA, Spasic M, Giurintano JP, Chan V, Daud AI, Ha P, Ye CJ, Roberts EW, Krummel MF | title = Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity | journal = Cell | volume = 177 | issue = 3 | pages = 556–571 | date = April 2019 | pmid = 30955881 | doi = 10.1016/j.cell.2019.02.005 | pmc = 6954108 }}</ref> Lung cancers have been found to include four different subsets of dendritic cells: three classical dendritic cell subsets and one plasmacytoid dendritic cell subset.<ref name="pmid30979687">{{cite journal | vauthors = Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, Krishnan I, Maroni G, Meyerovitz CV, Kerwin CM, Choi S, Richards WG, De Rienzo A, Tenen DG, Bueno R, Levantini E, Pittet MJ, Klein AM | title = Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species | journal = Immunity | volume = 50 | issue = 5 | pages = 1317–1334 | date = April 2019 | pmid = 30979687 | doi = 10.1016/j.immuni.2019.03.009 | pmc = 6620049 }}</ref> At least some of these dendritic cell subsets can activate CD4+ helper T cells and [[Cytotoxic T cell|CD8+ cytotoxic T cells]], which are immune cells that can also suppress [[tumor]] growth. However, dendritic cell activity is commonly suppressed by regulatory T cells and multiple other factors.<ref>{{cite journal | url=https://doi.org/10.1038/s41586-020-2134-y | doi=10.1038/s41586-020-2134-y | title=A conserved dendritic-cell regulatory program limits antitumour immunity | date=2020 | last1=Maier | first1=Barbara | last2=Leader | first2=Andrew M. | last3=Chen | first3=Steven T. | last4=Tung | first4=Navpreet | last5=Chang | first5=Christie | last6=Leberichel | first6=Jessica | last7=Chudnovskiy | first7=Aleksey | last8=Maskey | first8=Shrisha | last9=Walker | first9=Laura | last10=Finnigan | first10=John P. | last11=Kirkling | first11=Margaret E. | last12=Reizis | first12=Boris | last13=Ghosh | first13=Sourav | last14=d'Amore | first14=Natalie Roy | last15=Bhardwaj | first15=Nina | last16=Rothlin | first16=Carla V. | last17=Wolf | first17=Andrea | last18=Flores | first18=Raja | last19=Marron | first19=Thomas | last20=Rahman | first20=Adeeb H. | last21=Kenigsberg | first21=Ephraim | last22=Brown | first22=Brian D. | last23=Merad | first23=Miriam | journal=Nature | volume=580 | issue=7802 | pages=257–262 | pmid=32269339 | pmc=7787191 | bibcode=2020Natur.580..257M }}</ref> Dendritic cell stimulating treatments, such as dendritic cell based vaccinations, have been emerging as a treatment with varying success.<ref>{{Cite journal |last=Saxena |first=Mansi |last2=Bhardwaj |first2=Nina |date=February 2018 |title=Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment |url=https://linkinghub.elsevier.com/retrieve/pii/S2405803317302406 |journal=Trends in Cancer |language=en |volume=4 |issue=2 |pages=119–137 |doi=10.1016/j.trecan.2017.12.007 |pmc=5823288 |pmid=29458962}}</ref> In experimental models, dendritic cells have also been shown to contribute to the success of cancer immunotherapies, for example with the immune checkpoint blocker anti-PD-1.<ref name="pmid27775706">{{cite journal | vauthors = Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu EF, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM, Kumari S, Kelly RL, Kwan BH, Abraham W, Hu K, Mehta NK, Kauke MJ, Suh H, Cochran JR, Lauffenburger DA, Wittrup KD, Irvine DJ | title = Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses | journal = Nat Med | volume = 22 | issue =  12| pages = 1402–1410 | date = December 2016 | pmid = 27775706 | doi = 10.1038/nm.4200 | pmc= 5209798}}</ref><ref name="pmid30552023">{{cite journal | vauthors = Garris CS, Arlauckas SP, Kohler RH, Trefny MP, Garren S, Piot C, Engblom C, Pfirschke C, Siwicki M, Gungabeesoon J, Freeman GJ, Warren SE, Ong S, Browning E, Twitty CG, Pierce RH, Le MH, Algazi AP, Daud AI, Pai SI, Zippelius A, Weissleder R, Pittet MJ | title = Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12 | journal = Immunity | volume = 49 | issue = 6 | pages = 1148–1161 | date = December 2018 | pmid = 30552023 | doi = 10.1016/j.immuni.2018.09.024 | pmc= 6301092 }}</ref>

=== Autoimmunity ===
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]] and inflammatory bowel diseases ([[Crohn's disease]] and [[ulcerative colitis]]).<ref name=Baumgart>{{cite journal | vauthors = Baumgart DC, Metzke D, Schmitz J, Scheffold A, Sturm A, Wiedenmann B, Dignass AU | year = 2005 | title = Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells | journal = Gut | volume = 54 | issue = 2 | pages = 228–36 | pmid = 15647187 | doi = 10.1136/gut.2004.040360 | pmc = 1774844}}</ref><ref name=Baumgart2>{{cite journal | vauthors = Baumgart DC, Thomas S, Przesdzing I, Metzke D, Bielecki C, Lehmann SM, Lehnardt S, Dorffel Y, Sturm A, Scheffold A, Schmitz J, Radbruch A | year = 2009 | title = Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease | journal = Clin Exp Immunol | volume = 157 | issue = 3 | pages = 423–36 | pmid = 19664152 | doi = 10.1111/j.1365-2249.2009.03981.x | pmc = 2745038}}</ref><ref name=Baumgart3>{{cite journal | vauthors = Baumgart DC, Carding SR | year = 2007 | title = Inflammatory bowel disease: cause and immunobiology | journal = The Lancet | volume = 369 | issue = 9573 | pages = 1627–40 | pmid =  17499605 | doi = 10.1016/S0140-6736(07)60750-8| s2cid = 13544348 }}</ref>