Jump to content

CD83

From Wikipedia, the free encyclopedia

CD83
Identifiers
AliasesCD83,BL11, HB15, CD83 molecule
External IDsOMIM:604534;MGI:1328316;HomoloGene:3121;GeneCards:CD83;OMA:CD83 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9308

12522

Ensembl

ENSG00000112149

ENSMUSG00000015396

UniProt

Q01151

O88324

RefSeq (mRNA)

NM_004233
NM_001040280
NM_001251901

NM_001289915
NM_009856

RefSeq (protein)

NP_001035370
NP_001238830
NP_004224

NP_001276844
NP_033986

Location (UCSC)Chr 6: 14.12 – 14.14 MbChr 13: 43.94 – 43.96 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Dimeric CD83 extracellular domain structure

CD83(Cluster of Differentiation 83) is a humanproteinencoded by theCD83gene.[5]

Structure

[edit]

The membrane-bound form of CD83 consists of an extracellularV-type immunoglobulin-like domain,atransmembrane domainand a cytoplasmicsignalingtail. 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 humanchromosome6p23 and mouse chromosome 13. In humans, apromoter261 bp upstream consists of fiveNF-κBand threeinterferon regulatory factorbinding sites, reflecting the involvement of CD83 in inflammation,[7]as well as binding sites for thearyl hydrocarbon receptor.The latter also occur in anenhancersequence located 185 bp downstream, inside the secondintron,[8]and may suggest negative regulation of transcription by microbial metabolites produced in the gut.

Function

[edit]

The transmembrane domain of membrane-bound CD83 stabilizesMHC II,costimulatory moleculesandCD28in the membrane by antagonizing MARCH-familyE3 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, suggestingautocrineimmune regulation.[11]However, it contrasts with differences between the single expression of soluble CD83 onmonocytesand membrane-bound CD83 on activateddendritic cellsseems also as their good marker.[clarification needed][12]Soluble CD83 also binds toCD154,leading toT helpertype 2 lymphocyteapoptosisby suppression ofBcl-2 inhibitors.[13]

Positive selection

[edit]

The development ofthymocytesduring 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]

Regulatory T cells

[edit]
CD83 KO mouse T regulatory cells revealds proinflamatory phenotype compared with WT mouse
Role of CD83 in tolerance establishment balance

T regulatory cells(Tregcells) are present in two major populations: thymically induced and peripherally induced Tregcells. All Tregcells express theFoxp3transcription 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 Tregcell induction, as suggested by reduction of this population in a conditional knockout mouse lacking CD83 specifically in Tregcells, which results in a proinflammatory phenotype.[15]

CD83 deficiency also results in an imbalances in effector function of Tregcells, as decreased expression of the T helper type 2 cell transcription factorGATA3is also important forST2production.[16]

Activated Tregcells produce large amounts of soluble CD83, leading to downregulation ofIRAK-1at inflamed sites, downregulation oftoll-like receptorsignaling, 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 reducedCD4+T lymphocyte activation and reducedIL-12production.[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-dependentendosomeprocessing.[11]

B cells

[edit]

CD83 expression correlates with rate of activation ofB lymphocytesand 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]

See also

[edit]

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000112149–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000015396–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^"Entrez Gene: CD83 CD83 molecule".
  6. ^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.
  7. ^Stein MF, Lang S, Winkler TH, Deinzer A, Erber S, Nettelbeck DM, et al. (April 2013)."Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type- and maturation-specific activation of the human CD83 promoter in dendritic cells".Molecular and Cellular Biology.33(7): 1331–1344.doi:10.1128/MCB.01051-12.PMC3624272.PMID23339870.
  8. ^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.PMID32115260.
  9. ^Grosche L, Knippertz I, König C, Royzman D, Wild AB, Zinser E, et al. (17 April 2020)."The CD83 Molecule - An Important Immune Checkpoint".Frontiers in Immunology.11:721.doi:10.3389/fimmu.2020.00721.PMC7181454.PMID32362900.
  10. ^abvon Rohrscheidt J, Petrozziello E, Nedjic J, Federle C, Krzyzak L, Ploegh HL, et al. (August 2016)."Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83".The Journal of Experimental Medicine.213(9): 1685–1694.doi:10.1084/jem.20160316.PMC4995086.PMID27503071.
  11. ^abBates JM, Flanagan K, Mo L, Ota N, Ding J, Ho S, et al. (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.PMC4326976.PMID25204675.
  12. ^abChen L, Zhu Y, Zhang G, Gao C, Zhong W, Zhang X (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.PMC3219128.PMID22065790.
  13. ^Wu YJ, Song YN, Geng XR, Ma F, Mo LH, Zhang XW, et al. (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.PMC6949156.PMID31929750.
  14. ^Kadouri N, Nevo S, Goldfarb Y, Abramson J (April 2020). "Thymic epithelial cell heterogeneity: TEC by TEC".Nature Reviews. Immunology.20(4): 239–253.doi:10.1038/s41577-019-0238-0.PMID31804611.S2CID208622435.
  15. ^Doebbeler M, Koenig C, Krzyzak L, Seitz C, Wild A, Ulas T, et al. (June 2018)."CD83 expression is essential for Treg cell differentiation and stability".JCI Insight.3(11): e99712.doi:10.1172/jci.insight.99712.PMC6124443.PMID29875316.
  16. ^abMaitra U, Davis S, Reilly CM, Li L (May 2009)."Differential regulation of Foxp3 and IL-17 expression in CD4 T helper cells by IRAK-1".Journal of Immunology.182(9): 5763–5769.doi:10.4049/jimmunol.0900124.PMC4773027.PMID19380824.
  17. ^Ishido S, Matsuki Y, Goto E, Kajikawa M, Ohmura-Hoshino M (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.PMID20213309.S2CID10403102.
  18. ^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.
  19. ^Krzyzak L, Seitz C, Urbat A, Hutzler S, Ostalecki C, Gläsner J, et al. (May 2016)."CD83 Modulates B Cell Activation and Germinal Center Responses".Journal of Immunology.196(9): 3581–3594.doi:10.4049/jimmunol.1502163.PMID26983787.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=CD83&oldid=1248377160"