CD83
![](https://upload.wikimedia.org/wikipedia/commons/thumb/f/f7/CD83-protein-structure.jpg/220px-CD83-protein-structure.jpg)
CD83 (Cluster of Differentiation 83) is a human protein encoded by the CD83 gene.[5]
Structure
[edit]The membrane-bound form of CD83 consists of an extracellular V-type immunoglobulin-like domain, a transmembrane domain and a cytoplasmic signaling tail. A free soluble form consists of the immunoglobulin-like domain alone. Membrane-bound CD83 is expected to form trimers. Soluble CD83 is able to assemble into dodecameric complexes.[6]
Gene
[edit]The CD83 gene is located on human chromosome 6p23 and mouse chromosome 13. In humans, a promoter 261 bp upstream consists of five NF-
Function
[edit]The transmembrane domain of membrane-bound CD83 stabilizes MHC II, costimulatory molecules and CD28 in the membrane by antagonizing MARCH-family E3 ubiquitin ligases.[9][10]
Ligands
[edit]It is not clear what ligands interact with CD83, but membrane-bound CD83 may homotypically interact with the soluble form, suggesting autocrine immune regulation.[11] However, it contrasts with differences between the single expression of soluble CD83 on monocytes and membrane-bound CD83 on activated dendritic cells seems also as their good marker.[clarification needed][12] Soluble CD83 also binds to CD154, leading to T helper type 2 lymphocyte apoptosis by suppression of Bcl-2 inhibitors.[13]
Positive selection
[edit]The development of thymocytes during the positive-selection stage may be guided by CD83 expression on cortical thymic epithelial cells (cTECs). CD4+CD8+ double-positive thymocytes surrounded by specially differentiated cTECs called thymic nurse cells are tested for function of their
Regulatory T cells
[edit]![CD83 KO mouse T regulatory cells revealds proinflamatory phenotype compared with WT mouse](https://upload.wikimedia.org/wikipedia/commons/thumb/9/9d/Role_of_CD83_in_tolerance_estabilshment_balances.jpg/220px-Role_of_CD83_in_tolerance_estabilshment_balances.jpg)
T regulatory cells (Treg cells) are present in two major populations: thymically induced and peripherally induced Treg cells. All Treg cells express the Foxp3 transcription factor, establishing their suppressive phenotype. Foxp3 expression is not affected by loss of CD83 in a CD83 knockout mouse. In contrast, CD83 seems important for peripheral Treg cell induction, as suggested by reduction of this population in a conditional knockout mouse lacking CD83 specifically in Treg cells, which results in a proinflammatory phenotype.[15]
CD83 deficiency also results in an imbalances in effector function of Treg cells, as decreased expression of the T helper type 2 cell transcription factor GATA3 is also important for ST2 production.[16]
Activated Treg cells produce large amounts of soluble CD83, leading to downregulation of IRAK-1 at inflamed sites, downregulation of toll-like receptor signaling, and switching of inflammatory signals to tolerance establishment.[16]
Dendritic cells
[edit]CD83 expression is a marker for mature dendritic cells.[12] CD83 stabilizes MHC II on membrane by antagonizing MARCH E3 ubiquitin ligases. A MARCH1 knockout mouse shows accumulation of MHC II, which leads to reduced CD4+ T lymphocyte activation and reduced IL-12 production.[17] Conversely, a CD83 knockout mouse shows a reduction of MHC II and CD86, better response to bacterial infection, and higher production of IL-12 than in the wild type. CD83 seems to be an important regulator of dendritic cell phenotype and MHC II turnover, mediated by CD83-dependent endosome processing.[11]
B cells
[edit]CD83 expression correlates with rate of activation of B lymphocytes and it is under control of the B cell receptor, CD40, or Toll-like receptor activation, as in other lymphocytes, where CD83 is expressed upon stimulation. A CD83 knockout mouse shows upregulated proliferation of B lymphocytes, suggesting that CD83 acts as a brake on proliferation.[18] CD83 does not affect affinity maturation of antibodies, but its deficiency enhances immunoglobulin E class switching, suggesting that CD83 may be involved in allergy development and could be a therapeutic target for allergy treatment.[19]
See also
[edit]References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000112149 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015396 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: CD83 CD83 molecule".
- ^ Berchtold S, Jones T, Mühl-Zürbes P, Sheer D, Schuler G, Steinkasserer A (March 1999). "The human dendritic cell marker CD83 maps to chromosome 6p23". Annals of Human Genetics. 63 (Pt 2): 181–3. doi:10.1046/j.1469-1809.1999.6320181.x. PMID 10738529. S2CID 25338621.
- ^ Stein MF, Lang S, Winkler TH, Deinzer A, Erber S, Nettelbeck DM, et al. (April 2013). "Multiple interferon regulatory factor and NF-
κ B sites cooperate in mediating cell-type- and maturation-specific activation of the human CD83 promoter in dendritic cells". Molecular and Cellular Biology. 33 (7): 1331–44. doi:10.1128/MCB.01051-12. PMC 3624272. PMID 23339870. - ^ Michalski J, Deinzer A, Stich L, Zinser E, Steinkasserer A, Knippertz I (July 2020). "Quercetin induces an immunoregulatory phenotype in maturing human dendritic cells". Immunobiology. 225 (4): 151929. doi:10.1016/j.imbio.2020.151929. PMID 32115260.
- ^ Grosche, Linda; Knippertz, Ilka; König, Christina; Royzman, Dmytro; Wild, Andreas B.; Zinser, Elisabeth; Sticht, Heinrich; Muller, Yves A.; Steinkasserer, Alexander; Lechmann, Matthias (17 April 2020). "The CD83 Molecule – An Important Immune Checkpoint". Frontiers in Immunology. 11: 721. doi:10.3389/fimmu.2020.00721. PMC 7181454. PMID 32362900.
- ^ a b von Rohrscheidt, Julia; Petrozziello, Elisabetta; Nedjic, Jelena; Federle, Christine; Krzyzak, Lena; Ploegh, Hidde L.; Ishido, Satoshi; Steinkasserer, Alexander; Klein, Ludger (22 August 2016). "Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83". Journal of Experimental Medicine. 213 (9): 1685–1694. doi:10.1084/jem.20160316. PMC 4995086. PMID 27503071.
- ^ a b Bates, J M; Flanagan, K; Mo, L; Ota, N; Ding, J; Ho, S; Liu, S; Roose-Girma, M; Warming, S; Diehl, L (March 2015). "Dendritic cell CD83 homotypic interactions regulate inflammation and promote mucosal homeostasis". Mucosal Immunology. 8 (2): 414–428. doi:10.1038/mi.2014.79. PMC 4326976. PMID 25204675.
- ^ a b Chen, Liwen; Zhu, Yibei; Zhang, Guangbo; Gao, Chao; Zhong, Weixue; Zhang, Xueguang (15 November 2011). "CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2". Proceedings of the National Academy of Sciences of the United States of America. 108 (46): 18778–18783. doi:10.1073/pnas.1018994108. ISSN 1091-6490. PMC 3219128. PMID 22065790.
- ^ Wu, Yong-Jin; Song, Yan-Nan; Geng, Xiao-Rui; Ma, Fei; Mo, Li-Hua; Zhang, Xiao-Wen; Liu, Da-Bo; Liu, Zhi-Gang; Yang, Ping-Chang (2020). "Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property". International Journal of Biological Sciences. 16 (2): 216–227. doi:10.7150/ijbs.38722. PMC 6949156. PMID 31929750.
- ^ Kadouri, Noam; Nevo, Shir; Goldfarb, Yael; Abramson, Jakub (April 2020). "Thymic epithelial cell heterogeneity: TEC by TEC". Nature Reviews Immunology. 20 (4): 239–253. doi:10.1038/s41577-019-0238-0. PMID 31804611. S2CID 208622435.
- ^ Doebbeler, Marina; Koenig, Christina; Krzyzak, Lena; Seitz, Christine; Wild, Andreas; Ulas, Thomas; Baßler, Kevin; Kopelyanskiy, Dmitry; Butterhof, Alina; Kuhnt, Christine; Kreiser, Simon; Stich, Lena; Zinser, Elisabeth; Knippertz, Ilka; Wirtz, Stefan; Riegel, Christin; Hoffmann, Petra; Edinger, Matthias; Nitschke, Lars; Winkler, Thomas; Schultze, Joachim L.; Steinkasserer, Alexander; Lechmann, Matthias (7 June 2018). "CD83 expression is essential for Treg cell differentiation and stability". JCI Insight. 3 (11): e99712. doi:10.1172/jci.insight.99712. PMC 6124443. PMID 29875316.
- ^ a b Maitra, Urmila; Davis, Sarah; Reilly, Christopher M.; Li, Liwu (1 May 2009). "Differential Regulation of Foxp3 and IL-17 Expression in CD4 T Helper Cells by IRAK-1". The Journal of Immunology. 182 (9): 5763–5769. doi:10.4049/jimmunol.0900124. PMC 4773027. PMID 19380824.
- ^ Ishido, Satoshi; Matsuki, Yohei; Goto, Eiji; Kajikawa, Mizuho; Ohmura-Hoshino, Mari (March 2010). "MARCH-I: A new regulator of dendritic cell function". Molecules and Cells. 29 (3): 229–232. doi:10.1007/s10059-010-0051-x. PMID 20213309. S2CID 10403102.
- ^ Kretschmer, Birte; Kühl, Svenja; Fleischer, Bernhard; Breloer, Minka (May 2011). "Activated T cells induce rapid CD83 expression on B cells by engagement of CD40". Immunology Letters. 136 (2): 221–227. doi:10.1016/j.imlet.2011.01.013. PMID 21277328.
- ^ Krzyzak, Lena; Seitz, Christine; Urbat, Anne; Hutzler, Stefan; Ostalecki, Christian; Gläsner, Joachim; Hiergeist, Andreas; Gessner, André; Winkler, Thomas H.; Steinkasserer, Alexander; Nitschke, Lars (1 May 2016). "CD83 Modulates B Cell Activation and Germinal Center Responses". The Journal of Immunology. 196 (9): 3581–3594. doi:10.4049/jimmunol.1502163. PMID 26983787.
Further reading
[edit]- Lechmann M, Berchtold S, Hauber J, Steinkasserer A (June 2002). "CD83 on dendritic cells: more than just a marker for maturation". Trends in Immunology. 23 (6): 273–5. doi:10.1016/S1471-4906(02)02214-7. PMID 12072358.
- Zhou LJ, Schwarting R, Smith HM, Tedder TF (July 1992). "A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily". Journal of Immunology. 149 (2): 735–42. doi:10.4049/jimmunol.149.2.735. PMID 1378080. S2CID 24475187.
- Zhou LJ, Tedder TF (April 1995). "Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily". Journal of Immunology. 154 (8): 3821–35. doi:10.4049/jimmunol.154.8.3821. PMID 7706722. S2CID 24672615.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Kozlow EJ, Wilson GL, Fox CH, Kehrl JH (January 1993). "Subtractive cDNA cloning of a novel member of the Ig gene superfamily expressed at high levels in activated B lymphocytes". Blood. 81 (2): 454–61. doi:10.1182/blood.V81.2.454.454. PMID 8422464.
- de la Fuente MA, Pizcueta P, Nadal M, Bosch J, Engel P (September 1997). "CD84 leukocyte antigen is a new member of the Ig superfamily". Blood. 90 (6): 2398–405. doi:10.1182/blood.V90.6.2398. PMID 9310491.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Olavesen MG, Bentley E, Mason RV, Stephens RJ, Ragoussis J (December 1997). "Fine mapping of 39 ESTs on human chromosome 6p23-p25". Genomics. 46 (2): 303–6. doi:10.1006/geno.1997.5032. PMID 9417921.
- Twist CJ, Beier DR, Disteche CM, Edelhoff S, Tedder TF (1998). "The mouse Cd83 gene: structure, domain organization, and chromosome localization". Immunogenetics. 48 (6): 383–93. doi:10.1007/s002510050449. PMID 9799334. S2CID 19869850.
- Berchtold S, Mühl-Zürbes P, Heufler C, Winklehner P, Schuler G, Steinkasserer A (November 1999). "Cloning, recombinant expression and biochemical characterization of the murine CD83 molecule which is specifically upregulated during dendritic cell maturation". FEBS Letters. 461 (3): 211–6. doi:10.1016/S0014-5793(99)01465-9. PMID 10567699. S2CID 28053654.
- Scholler N, Hayden-Ledbetter M, Hellström KE, Hellström I, Ledbetter JA (March 2001). "CD83 is an I-type lectin adhesion receptor that binds monocytes and a subset of activated CD8+ T cells [corrected]". Journal of Immunology. 166 (6): 3865–72. doi:10.4049/jimmunol.166.6.3865. PMID 11238630.
- Fanales-Belasio E, Moretti S, Nappi F, Barillari G, Micheletti F, Cafaro A, Ensoli B (January 2002). "Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses". Journal of Immunology. 168 (1): 197–206. doi:10.4049/jimmunol.168.1.197. hdl:2108/188460. PMID 11751963. S2CID 25473321.
- Berchtold S, Mühl-Zürbes P, Maczek E, Golka A, Schuler G, Steinkasserer A (July 2002). "Cloning and characterization of the promoter region of the human CD83 gene". Immunobiology. 205 (3): 231–46. doi:10.1078/0171-2985-00128. PMID 12182451.
- te Velde AA, van Kooyk Y, Braat H, Hommes DW, Dellemijn TA, Slors JF, et al. (January 2003). "Increased expression of DC-SIGN+IL-12+IL-18+ and CD83+IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn's disease". European Journal of Immunology. 33 (1): 143–51. doi:10.1002/immu.200390017. PMID 12594843. S2CID 44959575.
- Dudziak D, Kieser A, Dirmeier U, Nimmerjahn F, Berchtold S, Steinkasserer A, et al. (August 2003). "Latent membrane protein 1 of Epstein-Barr virus induces CD83 by the NF-kappaB signaling pathway". Journal of Virology. 77 (15): 8290–8. doi:10.1128/JVI.77.15.8290-8298.2003. PMC 165234. PMID 12857898.
- Hock BD, Haring LF, Steinkasserer A, Taylor KG, Patton WN, McKenzie JL (March 2004). "The soluble form of CD83 is present at elevated levels in a number of hematological malignancies". Leukemia Research. 28 (3): 237–41. doi:10.1016/S0145-2126(03)00255-8. PMID 14687618.
- Sénéchal B, Boruchov AM, Reagan JL, Hart DN, Young JW (June 2004). "Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83". Blood. 103 (11): 4207–15. doi:10.1182/blood-2003-12-4350. PMID 14962896.
- Cao W, Lee SH, Lu J (January 2005). "CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells". The Biochemical Journal. 385 (Pt 1): 85–93. doi:10.1042/BJ20040741. PMC 1134676. PMID 15320871.
External links
[edit]- CD83+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CD83 genome location and CD83 gene details page in the UCSC Genome Browser.