The membrane-bound form of CD83 consists of an extracellularV-type immunoglobulin-like domain, atransmembrane domain and a cytoplasmicsignaling 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]
The CD83 gene is located on humanchromosome 6p23 and mouse chromosome 13. In humans, apromoter 261 bp upstream consists of fiveNF-κB and threeinterferon regulatory factor binding sites, reflecting the involvement of CD83 in inflammation,[7] as well as binding sites for thearyl hydrocarbon receptor. The latter also occur in anenhancer sequence located 185 bp downstream, inside the secondintron,[8] and may suggest negative regulation of transcription by microbial metabolites produced in the gut.
It is not clear what ligands interact with CD83, but membrane-bound CD83 may homotypically interact with the soluble form, suggestingautocrine immune regulation.[11] However, it contrasts with differences between the single expression of soluble CD83 onmonocytes and membrane-bound CD83 on activateddendritic cells seems also as their good marker.[clarification needed][12] Soluble CD83 also binds toCD154, leading toT helper type 2 lymphocyteapoptosis by suppression ofBcl-2 inhibitors.[13]
The development ofthymocytes during the positive-selection stage may be guided by CD83 expression oncortical thymic epithelial cells (cTECs).CD4+CD8+ double-positive thymocytes surrounded by specially differentiated cTECs called thymic nurse cells are tested for function of their αβT cell receptor (TCR); a nonreactive TCR leads to thymocyte death by neglect. Successful rearrangement of a reactive TCR supports survival and restriction of expression to CD4 or CD8 alone on single-positive thymocytes, depending on the ability to recognize MHC II orMHC I, respectively. Upregulation of MHC II turnover on thymic nurse cells by CD83 may enlarge the population of CD4+ single-positive thymocytes.[14][10]
T regulatory cells (Treg cells) are present in two major populations: thymically induced and peripherally induced Treg cells. All Treg cells express theFoxp3 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 factorGATA3 is also important forST2 production.[16]
Activated Treg cells produce large amounts of soluble CD83, leading to downregulation ofIRAK-1 at inflamed sites, downregulation oftoll-like receptor signaling, and switching of inflammatory signals to tolerance establishment.[16]
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 reducedCD4+ T lymphocyte activation and reducedIL-12 production.[17] Conversely, a CD83 knockout mouse shows a reduction of MHC II andCD86, 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-dependentendosome processing.[11]
CD83 expression correlates with rate of activation ofB lymphocytes and it is under control of theB 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]
^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):181–183.doi:10.1046/j.1469-1809.1999.6320181.x.PMID10738529.S2CID25338621.
^Kretschmer B, Kühl S, Fleischer B, Breloer M (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.PMID21277328.
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):273–275.doi:10.1016/S1471-4906(02)02214-7.PMID12072358.
Zhou LJ, Tedder TF (April 1995). "Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily".Journal of Immunology.154 (8):3821–3835.doi:10.4049/jimmunol.154.8.3821.PMID7706722.S2CID24672615.
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):171–174.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
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):149–156.doi:10.1016/S0378-1119(97)00411-3.PMID9373149.
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):303–306.doi:10.1006/geno.1997.5032.PMID9417921.
Twist CJ, Beier DR, Disteche CM, Edelhoff S, Tedder TF (1998). "The mouse Cd83 gene: structure, domain organization, and chromosome localization".Immunogenetics.48 (6):383–393.doi:10.1007/s002510050449.PMID9799334.S2CID19869850.
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):211–216.Bibcode:1999FEBSL.461..211B.doi:10.1016/S0014-5793(99)01465-9.PMID10567699.S2CID28053654.
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):231–246.doi:10.1078/0171-2985-00128.PMID12182451.
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