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CD83

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CD83
Identifiers
AliasesCD83, BL11, HB15, CD83 molecule
External IDsOMIM: 604534; MGI: 1328316; GeneCards: CD83
Orthologs
DatabasesNCBI: entry; OMA: entry
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
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CD83 (cluster of differentiation 83) is a cell-surface glycoprotein of the immunoglobulin superfamily encoded in humans by the CD83 gene.[5] It is expressed primarily by activated immune cells, including dendritic cells, T cells, B cells and regulatory T cells, as well as by microglia and cortical thymic epithelial cells (cTECs) in the thymus.[6][7] CD83 contributes to the regulation of immune responses, including the resolution of inflammation and the induction of immunological tolerance.

Crystal structure of the extracellular domain of the dimeric human sCD83 protein

Structure

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CD83 occurs in two biologically relevant forms:

  • Membrane-bound CD83 (mCD83) is a type I transmembrane protein comprising an extracellular V-type immunoglobulin-like domain, a transmembrane region and a short cytoplasmic signaling domain. It is expressed on activated immune cells and functions as an immunological checkpoint involved in the resolution of inflammation and in limiting excessive autoimmune responses.[6][7] Membrane-bound CD83 is thought to form trimers.
  • Soluble CD83 (sCD83) comprises the extracellular immunoglobulin-like domain alone and is shed from the surface of activated immune cells.[8] Soluble CD83 can assemble into dodecameric complexes and induces immunoregulatory processes, including the induction of tolerogenic dendritic cells, regulatory T cells (Treg cells) and pro-resolving macrophages.[7][9]

Both forms of CD83 are glycosylated. CD83 mRNA is transported from the cell nucleus to the cytosol through the export receptor CRM1.[6] The soluble form has structural similarities to B7-1, B7-2 and CD48.[10]

Gene

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The CD83 gene is located on the short arm of human chromosome 6 (6p23) and on mouse chromosome 13.[11] The human CD83 promoter extends approximately 261 base pairs upstream of the transcription start site and contains several binding sites for NF-κB and interferon regulatory factors. This organization reflects the integration of CD83 into signaling pathways controlled by cytokines and inflammatory mediators.[12]

Binding sites for the aryl hydrocarbon receptor (AhR) have also been identified in the promoter and in an enhancer region within the second intron.[13] This arrangement suggests that CD83 transcription may be negatively regulated by gut-derived microbial metabolites and other AhR ligands.

Function

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CD83 participates in the maturation, activation and homeostasis of B cells, T cells and dendritic cells.[14]

The transmembrane region of mCD83 stabilizes MHC II molecules, costimulatory molecules such as CD86, and CD28 in the plasma membrane by antagonizing MARCH-family E3 ubiquitin ligases.[7][15] By stabilizing these molecules, mCD83 regulates the efficiency of antigen presentation and subsequent T-cell activation.

Ligands

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The precise physiological ligands of mCD83 have not been fully characterized. Early binding studies showed that murine B cells,[16] human immature and mature dendritic cells,[17] and activated CD8+ T cells[18] can bind sCD83, but did not identify a specific individual receptor. mCD83 has also been reported to engage in homotypic interactions with the soluble form.[19]

Loss of mCD83 on immune cells is associated in preclinical models with excessive autoimmune responses in multiple sclerosis, rheumatoid arthritis, neuroinflammatory disease[20] and inflammatory bowel disease.[7][19]

sCD83 binds the TLR4/MD-2 complex on monocytes and osteoclasts. Through the TRIF signaling pathway, it activates indoleamine 2,3-dioxygenase (IDO), which produces the tryptophan metabolite kynurenine. Kynurenine in turn induces regulatory T cells, which can limit or resolve excessive immune responses.[7][9] In preclinical studies, sCD83 has also modulated allergic T-helper-cell type 2 immune responses, including in experimental allergic rhinitis, and reduced allograft rejection.[21]

Cd4+ t-cell selection in the thymus

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The development of CD4+ T cells during positive selection is regulated substantially by CD83 expression on cortical thymic epithelial cells (cTECs).[22][15] During positive selection, CD4+CD8+ double-positive thymocytes interact with cTECs through their T-cell receptors. A non-functional interaction results in cell death, whereas appropriate recognition permits survival and commitment to either the CD4 or CD8 lineage according to recognition of MHC II or MHC I, respectively. mCD83 inhibits the activity of the MHC-II-degrading MARCH8 E3 ubiquitin ligase in cTECs, thereby regulating MHC-II expression. Loss of CD83 in cTECs markedly reduces the peripheral CD4+ T-cell population.[15]

Regulatory t cells

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Role of CD83 in establishing immunological tolerance

Regulatory T cells (Treg cells) comprise thymically derived and peripherally induced populations. They express the transcription factor FOXP3, which establishes their suppressive phenotype. Although FOXP3 expression is unchanged in CD83 knockout mice, mCD83 is important for peripheral induction of Treg cells. Mice with Treg-cell-specific CD83 deficiency have reduced numbers of these cells and develop a pro-inflammatory phenotype with excessive autoimmune responses, including in experimental colitis.[23]

CD83 deletion also causes an imbalance in Treg-cell effector function, including decreased expression of GATA3, a transcription factor important for expression of the ST2 receptor.[23] Activated Treg cells also express and secrete sCD83, which can downregulate IRAK-1 in inflamed tissue and contribute to the induction of tolerance mechanisms.[24]

Dendritic cells

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CD83 expression is a classical marker of mature dendritic cells.[6] As in cTECs, CD83 stabilizes MHC-II expression in dendritic cells by antagonizing MARCH1 E3 ubiquitin ligases. Dendritic-cell-specific CD83 knockout mice show reduced surface MHC II and CD86, indicating that CD83 is a central regulator of dendritic-cell phenotype.[7] Specific deletion of CD83 in dendritic cells also leads to excessive autoimmune responses, including in a preclinical model of multiple sclerosis.[25]

B cells

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Expression of mCD83 correlates with B-lymphocyte activation and is regulated by signaling through the B-cell receptor, CD40 and Toll-like receptors. In B-cell-specific CD83 knockout mice, B-cell proliferation is increased.[26] mCD83 does not directly affect antibody affinity maturation, but promotes class switching to IgE, suggesting a role in the development of allergic responses and making CD83 a potential therapeutic target in allergy.[27]

sCD83 in hair growth and follicle regeneration

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Recent preclinical studies have identified soluble CD83 (sCD83) as a modulator of hair growth and regeneration of resting hair follicles. In preclinical models, sCD83 administration activated hair follicles and accelerated the transition from the resting telogen phase to the growth anagen phase.[28] A proposed multimodal mechanism involves the differentiation of macrophages towards pro-resolving M2 phenotypes and recruitment of regulatory T cells. These cell types can resolve inflammatory microenvironments around hair follicles and promote activation of resident hair-follicle stem cells.[29]

Transcriptomic analyses of human hair follicles indicate that sCD83 activates Wnt signaling and downregulates inhibitors of anagen growth, including Dkk-1. In ex vivo cultures of human hair follicles, sCD83 accelerated hair-shaft elongation, prolonged anagen and inhibited transition to telogen, in part through inhibition of apoptosis in hair follicles.[30]

In a preclinical model of alopecia areata, sCD83 reversed autoimmune hair loss and induced new hair growth; the proposed mechanism was IDO-mediated activation of regulatory T cells.[31] A scientific commentary also reported the first successful cosmetic use of an sCD83-based product in one individual.[32] In 2025, the European Patent Office granted a patent for the use of sCD83 in promoting hair growth and wound healing.[33]

See also

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References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000112149 – Ensembl, May 2017
  2. 1 2 3 GRCm38: 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". National Center for Biotechnology Information.
  6. 1 2 3 4 Prechtel AT, Steinkasserer A (May 2007). "CD83: an update on functions and prospects of the maturation marker of dendritic cells". Archives of Dermatological Research. 299 (2): 59–69. doi:10.1007/s00403-007-0743-z. PMID 17334966.
  7. 1 2 3 4 5 6 7 Grosche L, Knippertz I, König C, Royzman D, Wild AB, Zinser E, et al. (2020). "The CD83 Molecule - An Important Immune Checkpoint". Frontiers in Immunology. 11 721. doi:10.3389/fimmu.2020.00721. PMC 7181454. PMID 32362900.
  8. ↑ 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. PMID 10738529. S2CID 25338621.
  9. 1 2 Horvatinovich JM, Grogan EW, Norris M, Steinkasserer A, Lemos H, Mellor AL, et al. (March 2017). "Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes". Journal of Immunology. 198 (6). Baltimore: 2286–2301. doi:10.4049/jimmunol.1600802. PMC 5340622. PMID 28193829.
  10. ↑ Heilingloh CS, Klingl S, Egerer-Sieber C, Schmid B, Weiler S, Mühl-Zürbes P, et al. (April 2017). "Crystal Structure of the Extracellular Domain of the Human Dendritic Cell Surface Marker CD83". Journal of Molecular Biology. 429 (8): 1227–1243. doi:10.1016/j.jmb.2017.03.009. PMID 28315353.
  11. ↑ 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. PMID 9799334. S2CID 19869850.
  12. ↑ 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. PMC 3624272. PMID 23339870.
  13. ↑ 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.
  14. ↑ Breloer M, Fleischer B (April 2008). "CD83 regulates lymphocyte maturation, activation and homeostasis". Trends in Immunology. 29 (4): 186–194. doi:10.1016/j.it.2008.01.009. PMID 18329338.
  15. 1 2 3 von 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. PMC 4995086. PMID 27503071.
  16. ↑ Cramer SO, Trumpfheller C, Mehlhoop U, Moré S, Fleischer B, von Bonin A (September 2000). "Activation-induced expression of murine CD83 on T cells and identification of a specific CD83 ligand on murine B cells". International Immunology. 12 (9): 1347–1351. doi:10.1093/intimm/12.9.1347. PMID 10967030.
  17. ↑ Lechmann M, Krooshoop DJ, Dudziak D, Kremmer E, Kuhnt C, Figdor CG, et al. (December 2001). "The extracellular domain of CD83 inhibits dendritic cell-mediated T cell stimulation and binds to a ligand on dendritic cells". The Journal of Experimental Medicine. 194 (12): 1813–1821. doi:10.1084/jem.194.12.1813. PMC 2193561. PMID 11748282.
  18. ↑ Hirano N, Butler MO, Xia Z, Ansén S, von Bergwelt-Baildon MS, Neuberg D, et al. (February 2006). "Engagement of CD83 ligand induces prolonged expansion of CD8+ T cells and preferential enrichment for antigen specificity". Blood. 107 (4): 1528–1536. doi:10.1182/blood-2005-05-2073. PMC 1895420. PMID 16239433.
  19. 1 2 Bates 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. PMC 4326976. PMID 25204675.
  20. ↑ Sinner P, Peckert-Maier K, Mohammadian H, Kuhnt C, Draßner C, Panagiotakopoulou V, et al. (August 2023). "Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis". Nature Communications. 14 (1) 4601. doi:10.1038/s41467-023-40370-2. PMC 10393859. PMID 37528070.
  21. ↑ 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. PMC 6949156. PMID 31929750.
  22. ↑ Fujimoto Y, Tu L, Miller AS, Bock C, Fujimoto M, Doyle C, et al. (March 2002). "CD83 expression influences CD4+ T cell development in the thymus". Cell. 108 (6): 755–767. doi:10.1016/S0092-8674(02)00673-6. PMID 11955430.
  23. 1 2 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. PMC 6124443. PMID 29875316.
  24. ↑ Maitra 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). Baltimore: 5763–5769. doi:10.4049/jimmunol.0900124. PMC 4773027. PMID 19380824.
  25. ↑ Wild AB, Krzyzak L, Peckert K, Stich L, Kuhnt C, Butterhof A, et al. (October 2019). "CD83 orchestrates immunity toward self and non-self in dendritic cells". JCI Insight. 4 (20) e126246. doi:10.1172/jci.insight.126246. PMC 6824314. PMID 31527313.
  26. ↑ 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. PMID 21277328.
  27. ↑ 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). Baltimore: 3581–3594. doi:10.4049/jimmunol.1502163. PMID 26983787.
  28. ↑ Royzman D, Peckert-Maier K, Stich L, König C, Wild AB, Tauchi M, et al. (2022). "Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages". Frontiers in Immunology. 13 1012647. doi:10.3389/fimmu.2022.1012647. PMC 9564224. PMID 36248909.
  29. ↑ Peckert-Maier K, Wild AB, Sprißler L, Fuchs M, Beck P, Auger JP, et al. (2023). "Soluble CD83 modulates human-monocyte-derived macrophages toward alternative phenotype, function, and metabolism". Frontiers in Immunology. 14 1293828. doi:10.3389/fimmu.2023.1293828. PMC 10755915. PMID 38162675.
  30. ↑ "Our Science: Therapeutics". Mallia Therapeutics. Retrieved 7 August 2026.
  31. ↑ Wan S, Li Y, Liu X, Song X (July 2026). "Soluble CD83 reverses alopecia areata via IDO-mediated Treg cell activation". The British Journal of Dermatology ljag274. doi:10.1093/bjd/ljag274. PMID 42397957.
  32. ↑ Royzman D, Steinkasserer A (August 2026). "Expanding the therapeutic landscape of sCD83 in hair disorders". The British Journal of Dermatology ljag328. doi:10.1093/bjd/ljag328. PMID 42570012.
  33. ↑ EP patent 4135745, Steinkasserer A, Zinser E, Royzman D, "Scd83 for Wound Healing, Hair Growth, and Skin and Hair Care", published 2023-02-22, issued 2025-05-07, assigned to Friedrich Alexander Universitaet Erlangen Nuernberg

Further reading

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