Affinage

CD83

CD83 antigen · UniProt Q01151

Length
205 aa
Mass
23.0 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD83 is a type I transmembrane immunoglobulin-superfamily glycoprotein that acts as a central rheostat of antigen-presenting cell function and T cell tolerance, operating through both membrane-bound and soluble forms (PMID:21220452, PMID:28193829). Its membrane-bound form stabilizes surface MHC class II and CD86 by opposing E3 ubiquitin ligase-mediated turnover: the CD83 transmembrane domain blocks IL-10-driven MARCH1-mediated ubiquitination and degradation of these molecules in dendritic cells (PMID:21220452), and CD83 acts genetically upstream of MARCH8 in thymic epithelial cells, where deletion of March8 rescues the impaired CD4+ T cell selection of CD83 transmembrane mutants (PMID:27503069). This stromal/thymic CD83 function is required for CD4+ single-positive thymocyte development, since the requirement maps to the thymic environment rather than the thymocytes themselves (PMID:11955430), and CD83 likewise sustains surface MHC class II on peripheral B cells and DCs by limiting its internalization (PMID:17804692). Beyond antigen presentation, CD83 is cell-intrinsically required across multiple immune lineages — in B cells for germinal center composition and antibody responses (PMID:26983787), in regulatory T cells for differentiation and resolution of inflammation (PMID:29875316), and in DCs, macrophages, and microglia as a restraint on pro-inflammatory activation, with conditional deletion aggravating EAE, colitis, and autoimmunity while enhancing bacterial clearance (PMID:25204675, PMID:31527313, PMID:37528070, PMID:36875129). Membrane CD83 also functions in the immunological synapse, enhancing intracellular calcium release in interacting T cells (PMID:24436459) and transducing an inhibitory homotypic signal through suppression of p38α phosphorylation (PMID:25204675). The soluble form (generated by shedding and by alternative splicing) is immunosuppressive (PMID:11431426, PMID:15905506): it binds the TLR4 co-receptor MD-2 on CD14+ monocytes, triggering IRAK-1 degradation and COX-2–dependent induction of IDO, IL-10, and PGE2 that suppress T cell proliferation (PMID:22065790, PMID:28193829), an IDO/TGF-β axis that resolves autoimmune arthritis and uveitis in vivo (PMID:30050530, PMID:31001257). CD83 expression is controlled at the transcriptional level by an IRF/NF-κB ternary promoter complex driving maturation-specific induction (PMID:23339870) and post-transcriptionally by a coding-region RNA element that, via HuR and APRIL/ANP32B, directs CRM1-dependent nuclear export of CD83 mRNA (PMID:16484227, PMID:17178712); the protein is further regulated by GRAIL-mediated ubiquitination at cytoplasmic lysines K168/K183 (PMID:19542455) and by GRASP55-dependent glycosylation and surface trafficking through its C-terminal TELV motif (PMID:25701785).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Established that CD83 surface expression depends on a specialized nucleocytoplasmic step, revealing that CD83 mRNA export is rate-limiting for protein production.

    Evidence Pharmacological block of eIF-5A hypusination (GC7) and analysis of CD83 mRNA export plus DC-mediated T cell activation

    PMID:10790432

    Open questions at the time
    • Indirect pharmacological mechanism
    • cis-element and trans-factors not yet identified
    • did not define the export receptor
  2. 2001 High

    First defined the soluble CD83 ectodomain as a functional inhibitor, showing CD83 binds a non-homophilic ligand on DCs and suppresses DC maturation and T cell proliferation.

    Evidence Recombinant hCD83ext binding and DC maturation / T cell proliferation assays in vitro

    PMID:11748282

    Open questions at the time
    • Ligand identity not determined
    • in vitro only
    • molecular mechanism of inhibition unresolved
  3. 2001 Medium

    Characterized CD83 as an adhesion receptor with a sialylated counterreceptor, and showed soluble CD83 is generated by shedding rather than new synthesis.

    Evidence CD83-Ig fusion binding, neuraminidase treatment, immunoprecipitation of a 72-kDa counterreceptor, and shedding analysis by ELISA/Western with synthesis inhibition

    PMID:11238630 PMID:11431426

    Open questions at the time
    • 72-kDa counterreceptor not molecularly identified
    • shedding protease unknown
  4. 2002 High

    Demonstrated a non-redundant in vivo requirement for CD83 in thymic stroma for CD4+ T cell development, defining its developmental role.

    Evidence CD83-/- mice with reciprocal thymocyte/bone-marrow adoptive transfer and flow cytometry

    PMID:11955430

    Open questions at the time
    • Molecular mechanism in TECs not defined at this stage
    • did not connect to MHC II regulation
  5. 2005 Medium

    Resolved how soluble CD83 arises and functions, identifying splice variants encoding soluble protein, disulfide dimerization at C129, and intracellular trafficking through Golgi/recycling endosomes.

    Evidence RT-PCR splice variant mapping with recombinant protein MLR assays; C129S mutagenesis; immunofluorescence colocalization with endocytosis and cathepsin inhibition

    PMID:15721284 PMID:15746244 PMID:15905506

    Open questions at the time
    • Relative in vivo contribution of splicing vs shedding to sCD83 pool unclear
    • trafficking machinery only partly defined
  6. 2006 High

    Defined the post-transcriptional control of CD83, identifying a coding-region RNA element bound by HuR and the cofactor APRIL/ANP32B that routes the mRNA through CRM1-dependent export.

    Evidence RNA-binding assays, reporter constructs, RNAi, leptomycin B, dominant-negative Nup214, and APRIL phosphosite mutagenesis

    PMID:16484227 PMID:17178712

    Open questions at the time
    • Structural basis of HuR-element recognition unresolved
    • how this pathway is coupled to DC maturation signals unclear
  7. 2007 High

    Established CD83 as an intrinsic enhancer of DC immunostimulatory capacity and a stabilizer of surface MHC class II on B cells and DCs.

    Evidence siRNA knockdown in monocyte-derived DCs with T cell proliferation/cytokine readouts; CD83-/- mice with MHC II surface vs intracellular and internalization assays

    PMID:17442926 PMID:17804692

    Open questions at the time
    • Mechanism linking CD83 to reduced MHC II internalization not yet molecular
    • no ligase identified at this point
  8. 2009 High

    Identified the E3 ligase GRAIL as a regulator of CD83 protein stability, mapping ubiquitination to cytoplasmic K168/K183 and linking CD83 to T cell costimulation.

    Evidence GRAIL transduction and domain/lysine mutagenesis, ubiquitination and proteasome assays, RNAi rescue, and CD4+ T cell activation assays

    PMID:19542455

    Open questions at the time
    • In vivo relevance of GRAIL-CD83 axis not tested
    • stoichiometry of degradation unclear
  9. 2011 High

    Defined the dominant membrane mechanism by which CD83 sustains antigen presentation: its transmembrane domain antagonizes MARCH1-mediated ubiquitination of MHC II and CD86, while the soluble form was shown to act via monocyte COX-2/PGE2.

    Evidence ENU TM-domain mutant mice with MARCH1 ubiquitination and IL-10 assays; T cell assays with COX-2 inhibitor NS-398 and monocyte depletion/transwell

    PMID:21220452 PMID:22065790

    Open questions at the time
    • How the TM domain physically blocks MARCH1 unresolved
    • molecular target of sCD83 on monocytes not yet identified in 2011
  10. 2014 Medium

    Dissected CD83 transcriptional control and synapse signaling functions, defining an IRF/NF-κB promoter complex, a homotypic inhibitory signal via p38α, and enhancement of T cell calcium release.

    Evidence ChIP/EMSA/reporter/mutagenesis of the CD83 promoter; conditional DC-CD83 KO colitis model with truncation mutants and p38 assays; siRNA/antibody blocking with calcium imaging

    PMID:23339870 PMID:24436459 PMID:25204675

    Open questions at the time
    • Receptor mediating homotypic signal unidentified
    • link between calcium enhancement and downstream T cell fate unclear
  11. 2016 High

    Extended CD83's MARCH-antagonist role to thymic MARCH8 via genetic epistasis, and established a B cell-intrinsic requirement for activation and germinal center responses.

    Evidence March8/Cd83 double-mutant mice with TEC MHC II and T cell selection analysis; B cell-specific conditional KO with mixed bone marrow chimeras, GC and IgE analysis, Borrelia infection

    PMID:26983787 PMID:27503069

    Open questions at the time
    • Whether membrane CD83 directly contacts MARCH ligases is not shown
    • GC dark/light zone mechanism incompletely defined
  12. 2015 Medium

    Identified GRASP55 as a direct CD83 partner controlling glycosylation and surface trafficking via the C-terminal TELV motif.

    Evidence Yeast two-hybrid, co-IP, TELV-motif mutagenesis with glycosylation and surface expression readouts

    PMID:25701785

    Open questions at the time
    • Single-lab interaction without reciprocal in vivo validation
    • how glycosylation state alters CD83 function unclear
  13. 2017 Medium

    Identified the receptor for soluble CD83, showing it binds MD-2 within the TLR4/MD-2 complex on monocytes to drive IRAK-1 degradation and COX-2-dependent IDO/IL-10/PGE2.

    Evidence Binding assays identifying MD-2, IRAK-1 degradation, downstream mediator induction with COX-2 inhibition, and T cell assays

    PMID:28193829

    Open questions at the time
    • Direct structural sCD83-MD-2 interaction not solved
    • whether membrane CD83 uses the same receptor unknown
  14. 2018 Medium

    Established cell-intrinsic CD83 requirements in regulatory T cells and defined soluble CD83 tolerogenic mechanisms in autoimmunity through cytoskeletal/calcium synapse disruption.

    Evidence Treg-specific conditional KO with scRNA-seq and autoimmunity models; EAU model with sCD83 imaging of F-actin and calcium microdomains

    PMID:29875316 PMID:30050530

    Open questions at the time
    • Molecular sensor linking CD83 to Treg gene program unknown
    • synapse-disruption mechanism single-lab
  15. 2019 High

    Defined DC-intrinsic CD83 as a brake on T cell priming and supporter of Treg function, and the sCD83 IDO/TGF-β axis as a resolution pathway in arthritis.

    Evidence DC-specific conditional KO with bacterial infection and EAE models; AIA model with IDO inhibitor and anti-TGF-β blockade plus osteoclast/Treg readouts

    PMID:31001257 PMID:31527313

    Open questions at the time
    • How CD83 loss elevates DC IL-2/IL-12 mechanistically unresolved
    • in vivo source of IDO-inducing sCD83 receptor not pinpointed
  16. 2023 Medium

    Extended CD83's anti-inflammatory checkpoint role to tissue macrophages and microglia, showing it sustains alternatively activated/pro-resolving phenotypes.

    Evidence Macrophage- and microglia-specific conditional KO with STAT-6/receptor/cytokine and phagocytosis readouts, wound healing, scRNA-seq, and EAE

    PMID:36875129 PMID:37528070

    Open questions at the time
    • Whether CD83 acts membrane-intrinsically or via shedding in these cells unclear
    • direct molecular effectors downstream of CD83 in myeloid cells undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the membrane CD83 receptor/ligand mediating its costimulatory, calcium, and homotypic signals, and the structural basis for its antagonism of MARCH ligases, remain unresolved.
  • No defined membrane CD83 receptor despite multiple functional readouts
  • no structure of CD83-MARCH or CD83-MD-2 complexes
  • relative in vivo contribution of membrane vs soluble CD83 not partitioned

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005576 extracellular region 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 2
Partners
ANP32BCD86ELAVL1GORASP2MARCH1MARCH8MD-2RNF128
Complex memberships
TLR4/MD-2 co-receptor complex (soluble CD83 binding partner)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The extracellular Ig domain of CD83 (hCD83ext) binds a ligand expressed on both immature and mature dendritic cells; this binding is not homophilic (immature DCs do not express CD83 yet bind hCD83ext), and soluble hCD83ext inhibits DC maturation by downmodulating CD80 and CD83 expression, and inhibits DC-dependent allogeneic and peptide-specific T cell proliferation in a concentration-dependent manner in vitro. Recombinant protein expression of soluble extracellular domain; binding assays on immature and mature DCs; DC maturation assays; allogeneic and peptide-specific T cell proliferation assays The Journal of experimental medicine High 11748282
2002 CD83 expression by thymic epithelial and dendritic cells is required for CD4+ single-positive thymocyte development: CD83-/- mice show a specific block in CD4+ SP thymocyte generation resulting in 75-90% reduction in peripheral CD4+ T cells, predominantly naive. Wild-type thymocytes transferred into CD83-/- mice fail to develop into mature CD4+ T cells, while CD83-/- thymocytes develop normally in wild-type hosts, demonstrating the requirement is in the stromal/thymic environment. CD83-/- mouse model; adoptive transfer of thymocytes and bone marrow stem cells into CD83-/- vs. wild-type hosts; flow cytometric analysis of T cell subsets Cell High 11955430
2000 CD83 mRNA is transported from the nucleus to the cytoplasm via a specific CRM1-dependent nuclear export pathway. Inhibition of the hypusine modification of eIF-5A (by GC7) prevents CD83 surface expression by blocking nucleocytoplasmic translocation of CD83 mRNA, and this also significantly inhibits DC-mediated T lymphocyte activation. Pharmacological inhibition of hypusine formation (GC7); analysis of CD83 mRNA nuclear export; DC-mediated T cell activation assays The Journal of experimental medicine Medium 10790432
2001 CD83 is an adhesion receptor: a soluble CD83-Ig fusion protein binds peripheral blood monocytes and a subset of activated CD3+CD8+ T lymphocytes. Binding to the CD8+ T cell line HPB-ALL is neuraminidase-sensitive, implicating sialic acid modification of a 72-kDa counterreceptor. Full-length CD83 expressed by a transfected carcinoma line mediates CD83-dependent adhesion to HPB-ALL cells. CD83-Ig fusion protein binding assays; neuraminidase treatment; immunoprecipitation of 72-kDa counterreceptor; adhesion assays with CD83-transfected cells Journal of immunology Medium 11238630
2001 Soluble CD83 (sCD83) is released from membrane CD83-positive cells by shedding (not de novo synthesis during short-term culture) and is detectable in normal human sera. Both activated B cell lines and monocyte-derived DCs release sCD83 proportionally to their mCD83 expression level. sCD83-specific ELISA; Western blotting; inhibition of de novo protein synthesis; culture of B cell lines and monocyte-derived DCs International immunology Medium 11431426
2005 CD83 mRNA contains four alternative splice variants in unstimulated PBMCs; the smallest splice product can be efficiently translated into a soluble CD83 protein. Recombinant soluble CD83 from this variant strongly inhibits T cell proliferation in MLR. Stimulation with PHA, TNF-alpha, or LPS upregulates full-length CD83 transcript and downregulates two of the three smaller splice variants. RT-PCR identification of splice variants; recombinant protein expression; MLR T cell proliferation assay; stimulation with mitogens/cytokines Journal of immunology Medium 15905506
2005 CD83 forms dimers via an intermolecular disulfide bond at cysteine 129. Mutation of C129 to serine abolishes dimerization. The monomeric mutant inhibits CD83 surface upregulation during DC maturation and inhibits DC-mediated allogeneic T cell stimulation in vitro, indicating functional activity of the soluble form is retained as a monomer. Recombinant mutational analysis (C129S); biochemical analysis of dimerization; DC maturation assays; MLR allogeneic T cell stimulation assays Biochemical and biophysical research communications Medium 15721284
2006 CD83 mRNA expression is post-transcriptionally regulated via a novel cis-acting structured RNA element in its coding region that binds HuR. HuR binding does not affect mRNA stability but is required for cytoplasmic accumulation of CD83 transcripts via the CRM1 nuclear export pathway. RNAi knockdown of HuR reduces CD83 expression; inhibition of CRM1 (leptomycin B) or overexpression of defective Nup214/CAN similarly diminishes cytoplasmic CD83 mRNA. RNA-binding assays; transient transfection with post-transcriptional regulatory element reporters; RNA interference; leptomycin B treatment; dominant-negative Nup214 overexpression; mRNA stability assays The Journal of biological chemistry High 16484227
2006 APRIL (ANP32B), a protein ligand of HuR, contributes to nuclear export and subsequent translation of CD83 mRNA. RNAi knockdown of APRIL reduces CD83 expression. Phosphorylation of APRIL at threonine 244 regulates its nuclear export and thereby modulates the nucleocytoplasmic translocation of CD83 mRNA. In contrast, pp32 (ANP32A) is dispensable for CD83 expression. RNA interference (RNAi); identification of NLS and NES of APRIL; phosphorylation mapping (T244); CD83 expression analysis The Journal of biological chemistry Medium 17178712
2007 CD83 knockdown by siRNA in monocyte-derived dendritic cells significantly diminishes DC-mediated T cell proliferation and alters cytokine expression during T cell priming, establishing CD83 as an enhancer of DC-mediated T cell stimulation. This was demonstrated without the use of viral infection or pharmacological inhibitors. siRNA knockdown of CD83 in immature monocyte-derived DCs; electroporation for delivery; allogeneic T cell proliferation assay; cytokine expression analysis Journal of immunology Medium 17442926
2011 The transmembrane domain of CD83 blocks IL-10-driven, MARCH1-mediated ubiquitination and degradation of MHC class II and CD86 in dendritic cells. Mice with an ENU-induced mutation eliminating the CD83 transmembrane region show reduced surface MHC class II and CD86, demonstrating that the CD83 TM domain enhances MHC class II and CD86 expression by opposing MARCH1-dependent turnover. ENU mutagenesis screen generating TM-domain CD83 mutant mice; analysis of MHC class II and CD86 surface expression; MARCH1-dependent ubiquitination assays; IL-10 treatment The Journal of experimental medicine High 21220452
2016 MARCH8 is the E3 ubiquitin ligase responsible for regulating surface MHC II in thymic epithelial cells (TECs). CD83 controls the ubiquitination of MHC II by MARCH8 in TECs: mice with the Cd83 anu/anu mutation (lacking functional CD83 TM domain) have impaired CD4+ T cell selection, and deletion of March8 in Cd83 anu/anu mice restores CD4+ T cell selection to normal levels, placing CD83 upstream of MARCH8-mediated MHC II regulation in TECs. March8-/- mice; Cd83 anu/anu mice; March8/Cd83 double-mutant mice; flow cytometric analysis of MHC II on cortical and medullary TECs; CD4+ T cell development and repertoire analysis The Journal of experimental medicine High 27503069
2009 GRAIL, a transmembrane RING finger E3 ubiquitin ligase, ubiquitinates CD83 on lysine residues K168 and K183 (but not K192) in its cytoplasmic domain, leading to proteasomal degradation of CD83 on CD4+ T cells. GRAIL-mediated CD83 downregulation requires an intact extracellular protease-associated domain and an enzymatically active RING domain. GRAIL knockdown by RNAi elevates CD83 levels, and CD83 expression on CD4+ T cells contributes to T cell activation as a costimulatory molecule. Retroviral transduction of GRAIL; GRAIL domain mutants; ubiquitination assays identifying K168/K183; proteasome pathway analysis; RNAi knockdown of GRAIL; CD4+ T cell activation assays Journal of immunology High 19542455
2003 EBV latent membrane protein 1 (LMP1) induces CD83 expression in B cells via NF-κB signaling. LMP1-mediated activation of the CD83 promoter is dependent on NF-κB, as shown by luciferase reporter assays using the CD83 promoter and LMP1 signaling mutants. Fusion constructs of the LMP1 TM domain with intracellular signaling domains of CD40, TNF-R1, or TNF-R2 similarly transactivate the CD83 promoter via NF-κB. Luciferase reporter assays with CD83 promoter; LMP1 signaling mutants; inducible LMP1 expression system; NF-κB pathway analysis Journal of virology Medium 12857898
2013 The human CD83 promoter activity in DCs is regulated by a ternary transcriptional complex consisting of an upstream regulatory element, a minimal promoter, and an enhancer containing IRF- and NF-κB binding sites. IRF-1, IRF-2, IRF-5, p50, p65, and cRel regulate maturation-specific CD83 expression; mutation of any IRF-binding site causes significant loss of promoter activity, while NF-κB overexpression enhances transcription. ChIP-on-chip microarray; biocomputational analysis; luciferase reporter assays; EMSA; ChIP with specific TF antibodies; site-directed mutagenesis of IRF-binding sites; NF-κB overexpression Molecular and cellular biology High 23339870
2007 CD83 expression by thymic stromal cells influences MHC class II surface expression on B cells, DCs, thymic epithelial cells, and peritoneal macrophages: CD83-/- mice show 25-50% reduction in surface MHC class II on splenic B cells and DCs due to increased internalization of class II from the surface of CD83-/- B cells. MHC class II transcription, intracellular expression, heterodimer structure, antigen processing, and antigen presentation are normal. CD83-/- mice; flow cytometry for MHC class II surface and intracellular expression; MHC class II internalization assays; MHC class II transcription analysis; antigen processing/presentation assays International immunology High 17804692
2008 CD83 expression on CD4+ T cells confers immunosuppressive function: retroviral transduction of CD83 into naive CD4+CD25- T cells induces a regulatory phenotype accompanied by Foxp3 induction. CD83+Foxp3+ T cells suppress the effector phase of contact hypersensitivity in vivo and prevent paralysis in experimental autoimmune encephalomyelitis (EAE), associated with suppression of IFN-gamma and IL-17 and increase in IL-10. Retroviral transduction of CD83 into naive CD4+ T cells; in vitro functional assays; adoptive transfer into contact hypersensitivity and EAE mouse models; cytokine analysis Journal of immunology Medium 18424708
2011 CD83 inhibits T cell proliferation and cytokine (IL-2, IFN-γ) production via monocytes: CD83 stimulates monocytes to produce prostaglandin E2 (PGE2) via NF-κB-dependent upregulation of COX-2. COX-2-selective inhibitor NS-398 fully prevents CD83-triggered inhibition of T cell responses, and neither IL-10 nor TGF-β mediates this effect. T cell proliferation assays; cytokine measurement (IL-2, IFN-γ, PGE2); COX-2 inhibitor (NS-398); NF-κB activation analysis; depletion of monocytes; transwell assays Proceedings of the National Academy of Sciences of the United States of America Medium 22065790
2017 Soluble CD83 (sCD83) binds to myeloid differentiation factor-2 (MD-2), the co-receptor within the TLR4/MD-2 complex, on CD14+ monocytes. This binding rapidly degrades IRAK-1 and induces anti-inflammatory mediators IDO, IL-10, and PGE2 in a COX-2-dependent manner, leading to inhibition of T cell proliferation and IL-2 secretion and T cell unresponsiveness to further differentiation signals. Binding assays identifying MD-2 as sCD83 partner; IRAK-1 degradation assays; IDO/IL-10/PGE2 induction assays; COX-2 inhibition; T cell proliferation and cytokine assays Journal of immunology Medium 28193829
2014 CD83 engages in homotypic cell-cell contact interactions that inhibit pro-inflammatory DC responses. CD83 knockdown or cytoplasmic truncation abrogates the effects of homotypic binding. The inhibitory signal transduced by CD83 homotypic interaction operates via the MAPK pathway by inhibiting p38α phosphorylation. Conditional DC-specific CD83 KO mice develop exacerbated colitis, while mucosal CD83 overexpression protects against colitis. Conditional DC-specific CD83 KO mice; CD83 cytoplasmic truncation mutants; siRNA knockdown; colitis model (DSS); p38α phosphorylation assays; cell-cell contact assays; transwell controls Mucosal immunology Medium 25204675
2005 CD83 protein localizes to the Golgi compartment and recycling endosomes in both immature and mature DCs. In immature DCs, CD83 cycles between endosomes and the cell surface; inhibition of endocytosis induces CD83 surface expression in immature DCs. During DC maturation, CD83 co-localizes with MHC class II in endocytic vesicles (exclusive to mature DCs), and the increase in surface CD83 results primarily from increased protein synthesis with contribution from regulated intracellular transport. Cathepsin inhibitors impair CD83 surface upregulation. Immunofluorescence co-localization with organelle markers; endocytosis inhibition; pulse-chase/protein synthesis analysis; cathepsin inhibitors; fractionation; live-cell imaging International immunology Medium 15746244
2015 GRASP55 interacts with CD83 in human dendritic cells, binding via the C-terminal TELV-motif of CD83. Mutation of the TELV-motif disrupts GRASP55 binding, alters CD83 glycosylation pattern, and reduces CD83 membrane surface expression. GRASP55 interaction with CD83 is induced during DC maturation and plays a role in CD83 glycosylation and surface trafficking. Yeast two-hybrid screening; co-immunoprecipitation; TELV-motif mutagenesis; glycosylation analysis; co-localization studies; DC maturation assays Biochemical and biophysical research communications Medium 25701785
2016 B cell-intrinsic CD83 is required for normal MHC class II and CD86 upregulation and B cell proliferation after stimulation. In vivo, B cell-specific CD83 conditional KO causes a shift in germinal center dark zone/light zone composition, an enhanced IgE response, and a competitive disadvantage in GC responses in mixed bone marrow chimeras. CD83 B-cKO mice show impaired bacterial clearance of Borrelia burgdorferi with a shift toward Th2 responses. B cell-specific CD83 conditional KO mice (CD83 B-cKO); mixed bone marrow chimeras; immunization experiments; germinal center analysis; IgG/IgE measurements; Borrelia burgdorferi infection model Journal of immunology High 26983787
2018 Treg-intrinsic CD83 expression is essential for Treg differentiation upon activation. Treg-specific conditional CD83 KO mice show a pro-inflammatory phenotype, downregulation of Treg-specific differentiation markers, induction of an inflammatory profile, aggravated autoimmunity, and impaired resolution of inflammation. Treg-specific conditional CD83 KO mice; single-cell RNA-sequencing; flow cytometry for Treg markers; autoimmunity models; inflammatory resolution assays JCI insight Medium 29875316
2019 DC-specific deletion of CD83 (CD83ΔDC) results in elevated IL-2 production, increased CD25 and OX40L expression on DCs, enhanced antigen-specific T cell responses, compromised Treg suppressive functions, and reduced peripheral Treg numbers. In bacterial infection models, CD83ΔDC mice clear Salmonella typhimurium and Listeria monocytogenes more efficiently with increased DC IL-12. In EAE, autoimmune inflammation is dramatically aggravated with increased CNS cell influx and Th17 numbers. DC-specific conditional CD83 KO (CD83ΔDC) mice; bacterial infection (Salmonella, Listeria); EAE model; cytokine profiling; T cell subset analysis; Treg functional assays JCI insight High 31527313
2023 CD83 in murine microglia restrains neuroinflammation: conditional deletion of CD83 in microglia results in an over-activated microglial state during EAE neuroinflammation, increased recruitment of pathogenic immune cells to the CNS, deterioration of resolving mechanisms, and exacerbated disease. CD83 expression is associated with pro-resolving microglial functions. Conditional CD83 KO in microglia; single-cell RNA-sequencing; EAE model; immune cell infiltration analysis; cytokine profiling Nature communications Medium 37528070
2023 CD83 functions as an immune checkpoint in macrophages: IL-4-stimulated alternatively activated macrophages express CD83, and conditional CD83 deletion in macrophages reduces inhibitory receptors (CD200R, MSR-1), decreases phagocytic capacity, reduces pSTAT-6 levels and Gata3 expression, increases pro-inflammatory mediators (TNF-α, IL-6, CXCL1, G-CSF), and enhances allo-reactive T cell stimulation with reduced Treg induction. In a wound healing model, CD83-deficient macrophages show increased inflammatory transcripts and altered tissue reconstitution. Conditional CD83 KO in macrophages (cKO); IL-4 stimulation; STAT-6 phosphorylation assays; cytokine measurement; phagocytosis assays; T cell proliferation assays; full-thickness excision wound healing model; gene expression analysis Frontiers in immunology Medium 36875129
2018 Soluble CD83 alleviates experimental autoimmune uveitis (EAU) by inducing tolerogenic DCs through disruption of cytoskeletal (filamentous actin) rearrangements at the DC-T cell contact zone, leading to altered calcium microdomain localization and suppressed co-stimulatory molecule synaptic expression and calcium responses in DCs. EAU mouse model; flow cytometry; imaging studies of cytoskeletal rearrangements; calcium response assays in DCs; systemic and topical sCD83 application; co-stimulatory molecule expression analysis Frontiers in immunology Medium 30050530
2019 Soluble CD83 enhances resolution of autoimmune antigen-induced arthritis via IDO induction: inhibition of IDO by 1-methyltryptophan completely abrogates sCD83 effects. TGF-β also mediates sCD83-induced reduction of bone destruction and cartilage damage. sCD83 reduces IL-17A, IFNγ, IL-6, TNFα, and RANKL expression, inhibits osteoclast differentiation, and increases regulatory T cell numbers in an IDO-TGF-β-dependent manner. Antigen-induced arthritis (AIA) mouse model; IDO inhibition (1-methyltryptophan); anti-TGF-β antibody blocking; cytokine quantification; osteoclast differentiation assays; Treg analysis Frontiers in immunology Medium 31001257
2004 CD38 engagement by agonistic anti-CD38 mAb on mature monocyte-derived DCs induces upregulation of CD83 expression and IL-12 secretion. Disruption of the CD38/CD31 interaction inhibits CD83 expression, IL-12 secretion, and MDDC-induced allogeneic T cell proliferation. CD38 is enzymatically active (cyclic ADP ribose synthesis) in mature DCs and its expression is NF-κB dependent. Anti-CD38 agonistic mAb stimulation; CD38/CD31 blocking; CD83 expression analysis; IL-12 secretion assays; T cell proliferation assays; NF-κB inhibition European journal of immunology Medium 15114667
2011 Activated T cells induce rapid CD83 expression on B cells via CD40 engagement: in vivo T cell activation induces CD83 on ~80% of B cells in draining lymph nodes without requiring TCR/MHC binding (antigen-non-specific bystander effect). This induction requires cell contact and is blocked by anti-CD40L antibody, demonstrating CD40-dependent, contact-mediated CD83 induction on B cells. T cell receptor transgenic mice; cognate peptide injection; CD40L-blocking antibody; transwell separation assays; MHC-mismatched co-culture controls; flow cytometry Immunology letters Medium 21277328
2014 Membrane CD83 on mature DCs enhances intracellular calcium release in T lymphocytes during DC-T cell interaction. siRNA knockdown of CD83 or antibody blocking of surface CD83 on mature DCs reduces both calcium signal amplitude and the proportion of responding T cells, and abrogates T cell signaling in the absence of extracellular calcium, indicating CD83 promotes calcium release from intracellular stores. siRNA knockdown; anti-CD83 mAb blocking; calcium indicator (Fluo-4-AM); flow cytometry; confocal microscopy; CFSE proliferation assay; calcium-free medium experiments Journal of leukocyte biology Medium 24436459

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. Journal of immunology (Baltimore, Md. : 1950) 641 7706722
2010 Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer research 330 20484028
2005 IL-18-induced CD83+CCR7+ NK helper cells. The Journal of experimental medicine 236 16203865
2002 CD83 on dendritic cells: more than just a marker for maturation. Trends in immunology 192 12072358
2011 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. The Journal of experimental medicine 188 21220452
2002 CD83 expression influences CD4+ T cell development in the thymus. Cell 174 11955430
2007 CD83 expression on dendritic cells and T cells: correlation with effective immune responses. European journal of immunology 168 17301951
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 157 11748282
2000 Human decidua contains potent immunostimulatory CD83(+) dendritic cells. The American journal of pathology 145 10880386
2019 CD83: Activation Marker for Antigen Presenting Cells and Its Therapeutic Potential. Frontiers in immunology 139 31231400
2000 Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA. The Journal of experimental medicine 122 10790432
2008 Rheumatoid arthritis synovium contains two subsets of CD83-DC-LAMP- dendritic cells with distinct cytokine profiles. The American journal of pathology 120 18292234
2007 CD83: an update on functions and prospects of the maturation marker of dendritic cells. Archives of dermatological research 120 17334966
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 115 12594843
2000 Expression of CCR6 and CD83 by cytokine-activated human neutrophils. Blood 115 11090084
2001 A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera. International immunology 114 11431426
2020 The CD83 Molecule - An Important Immune Checkpoint. Frontiers in immunology 110 32362900
2008 CD83 regulates lymphocyte maturation, activation and homeostasis. Trends in immunology 99 18329338
2007 CD83 knockdown in monocyte-derived dendritic cells by small interfering RNA leads to a diminished T cell stimulation. Journal of immunology (Baltimore, Md. : 1950) 98 17442926
2002 Cutting edge: CD83 regulates the development of cellular immunity. Journal of immunology (Baltimore, Md. : 1950) 90 11884422
2001 CD83 is an I-type lectin adhesion receptor that binds monocytes and a subset of activated CD8+ T cells [corrected]. Journal of immunology (Baltimore, Md. : 1950) 83 11238630
2016 CD83 Modulates B Cell Activation and Germinal Center Responses. Journal of immunology (Baltimore, Md. : 1950) 80 26983787
2007 CD83 expression is a sensitive marker of activation required for B cell and CD4+ T cell longevity in vivo. Journal of immunology (Baltimore, Md. : 1950) 80 17878352
2004 CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction. European journal of immunology 72 15114667
1999 Cloning, recombinant expression and biochemical characterization of the murine CD83 molecule which is specifically upregulated during dendritic cell maturation. FEBS letters 71 10567699
2002 Role of CD83 in the immunomodulation of dendritic cells. International archives of allergy and immunology 69 12403928
2002 Up-regulation of the dendritic cell marker CD83 on polymorphonuclear neutrophils (PMN): divergent expression in acute bacterial infections and chronic inflammatory disease. Clinical and experimental immunology 69 12452842
2006 Expression of CD83 is regulated by HuR via a novel cis-active coding region RNA element. The Journal of biological chemistry 66 16484227
2008 CD83 expression in CD4+ T cells modulates inflammation and autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 65 18424708
2004 Homologs of CD83 from elasmobranch and teleost fish. Journal of immunology (Baltimore, Md. : 1950) 64 15383588
2016 Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection. The Journal of experimental medicine 61 27503069
2009 Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease. The Journal of experimental medicine 61 19171763
2001 Human monocyte-derived and CD83(+) blood dendritic cells enhance NK cell-mediated cytotoxicity. European journal of immunology 60 11536161
2017 Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes. Journal of immunology (Baltimore, Md. : 1950) 57 28193829
2006 CD83: a regulatory molecule of the immune system with great potential for therapeutic application. Journal of medical and dental sciences 57 16913569
2004 The soluble form of CD83 is present at elevated levels in a number of hematological malignancies. Leukemia research 57 14687618
2006 Analysis of nucleocytoplasmic trafficking of the HuR ligand APRIL and its influence on CD83 expression. The Journal of biological chemistry 53 17178712
1998 The mouse Cd83 gene: structure, domain organization, and chromosome localization. Immunogenetics 53 9799334
2005 Alternative splicing generates putative soluble CD83 proteins that inhibit T cell proliferation. Journal of immunology (Baltimore, Md. : 1950) 52 15905506
2001 Calcium signaling inhibits interleukin-12 production and activates CD83(+) dendritic cells that induce Th2 cell development. Blood 52 11588047
2000 Activation-induced expression of murine CD83 on T cells and identification of a specific CD83 ligand on murine B cells. International immunology 52 10967030
2018 CD83 expression is essential for Treg cell differentiation and stability. JCI insight 51 29875316
2007 CD83 is a regulator of murine B cell function in vivo. European journal of immunology 49 17266176
2007 Dendritic cell CD83: a therapeutic target or innocent bystander? Immunology letters 47 18001846
2007 A limited course of soluble CD83 delays acute cellular rejection of MHC-mismatched mouse skin allografts. Transplant international : official journal of the European Society for Organ Transplantation 45 17291220
2007 CD83 influences cell-surface MHC class II expression on B cells and other antigen-presenting cells. International immunology 45 17804692
2020 Human CD83-targeted chimeric antigen receptor T cells prevent and treat graft-versus-host disease. The Journal of clinical investigation 44 32437331
2014 Soluble CD83 ameliorates experimental colitis in mice. Mucosal immunology 43 24424524
2009 Neuronal expression of Cd36, Cd44, and Cd83 antigen transcripts maps to distinct and specific murine brain circuits. The Journal of comparative neurology 43 19844997
2007 CD83 modulates B cell function in vitro: increased IL-10 and reduced Ig secretion by CD83Tg B cells. PloS one 43 17710154
2008 A highly phagocytic cell line TO from Atlantic salmon is CD83 positive and M-CSFR negative, indicating a dendritic-like cell type. Fish & shellfish immunology 41 18817880
1997 Hodgkin's cells express CD83, a dendritic cell lineage associated antigen. Pathology 41 9271021
2023 Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis. Nature communications 40 37528070
2009 Decreased small airway and alveolar CD83+ dendritic cells in COPD. Chest 40 19465512
2004 A novel mutation in CD83 results in the development of a unique population of CD4+ T cells. Journal of immunology (Baltimore, Md. : 1950) 40 15322158
2001 Diverse functional activity of CD83+ monocyte-derived dendritic cells and the implications for cancer vaccines. Critical reviews in immunology 40 11642602
2014 Dendritic cell CD83 homotypic interactions regulate inflammation and promote mucosal homeostasis. Mucosal immunology 39 25204675
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 39 22065790
2003 Latent membrane protein 1 of Epstein-Barr virus induces CD83 by the NF-kappaB signaling pathway. Journal of virology 38 12857898
2017 The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways. Journal of virology 37 28659471
2015 An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the decidua of women with recurrent spontaneous abortion. European journal of medical research 37 25563385
2009 The transmembrane E3 ligase GRAIL ubiquitinates and degrades CD83 on CD4 T cells. Journal of immunology (Baltimore, Md. : 1950) 37 19542455
2021 Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83. Frontiers in immunology 36 34531862
2019 CD83 orchestrates immunity toward self and non-self in dendritic cells. JCI insight 36 31527313
2007 Unique features and distribution of the chicken CD83+ cell. Journal of immunology (Baltimore, Md. : 1950) 36 17911597
2002 Upregulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal disease. Journal of periodontal research 34 12113551
2001 Detection of anaphylatoxin receptors on CD83+ dendritic cells derived from human skin. Immunology 34 11412308
2014 Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo. Immunobiology 32 25151500
2005 CD83 is a dimer: Comparative analysis of monomeric and dimeric isoforms. Biochemical and biophysical research communications 32 15721284
2005 CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells. International immunology 32 15746244
2003 Enhanced activation of CD83-positive T cells. Scandinavian journal of immunology 32 12950676
2016 The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population. Journal of immunology (Baltimore, Md. : 1950) 31 27837105
2008 The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populations in vivo. Proceedings of the National Academy of Sciences of the United States of America 31 18701714
2003 Expression of CD83 in the murine immune system. Medical microbiology and immunology 31 12687354
2002 Overexpression, purification, and biochemical characterization of the extracellular human CD83 domain and generation of monoclonal antibodies. Protein expression and purification 31 11922761
2007 CD83 gene polymorphisms increase susceptibility to human invasive cervical cancer. Cancer research 30 18056445
2023 CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation. Frontiers in immunology 29 36875129
2019 Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner. Frontiers in immunology 29 31001257
2006 Enhanced T-cell activation and T-cell-dependent IL-2 production by CD83+, CD25high, CD43high human monocyte-derived dendritic cells. Molecular immunology 29 17023048
2019 Rainbow Trout Red Blood Cells Exposed to Viral Hemorrhagic Septicemia Virus Up-Regulate Antigen-Processing Mechanisms and MHC I&II, CD86, and CD83 Antigen-presenting Cell Markers. Cells 28 31035565
2015 CD83 is required for the induction of protective immunity by a DNA vaccine in a teleost model. Developmental and comparative immunology 28 25800093
2015 Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. Leukemia 27 26286117
2011 Activated T cells induce rapid CD83 expression on B cells by engagement of CD40. Immunology letters 27 21277328
1998 Low CD83, but normal MHC class II and costimulatory molecule expression, on spleen dendritic cells from HIV+ patients. AIDS research and human retroviruses 27 9566553
2018 CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma. Haematologica 26 29351987
2014 Dendritic cell membrane CD83 enhances immune responses by boosting intracellular calcium release in T lymphocytes. Journal of leukocyte biology 26 24436459
2023 CD83 Regulates the Immune Responses in Inflammatory Disorders. International journal of molecular sciences 24 36769151
2018 Soluble CD83 Alleviates Experimental Autoimmune Uveitis by Inhibiting Filamentous Actin-Dependent Calcium Release in Dendritic Cells. Frontiers in immunology 24 30050530
2009 Engagement of CD83 on B cells modulates B cell function in vivo. Journal of immunology (Baltimore, Md. : 1950) 24 19234177
2015 CD1a+ and CD83+ Langerhans cells are reduced in lower lip squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 23 26661374
2010 Expression of Scophthalmus maximus CD83 correlates with bacterial infection and antigen stimulation. Fish & shellfish immunology 23 20561589
2002 In situ localization of CD83-positive dendritic cells in psoriatic lesions. Dermatology (Basel, Switzerland) 22 11937733
2022 Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation. International journal of molecular sciences 20 35054916
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 20 23339870
2013 Differentiation and activation of equine monocyte-derived dendritic cells are not correlated with CD206 or CD83 expression. Immunology 20 23461413
2008 CD83 regulates splenic B cell maturation and peripheral B cell homeostasis. International immunology 20 18544574
2007 Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible by commensal bacteria and suppress allergen-induced human neonatal Th2 differentiation. Infection and immunity 20 17526743
2017 Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-α therapy. Cytokine 19 28267648
2015 CD83 and GRASP55 interact in human dendritic cells. Biochemical and biophysical research communications 19 25701785
2015 Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vγ9Vδ2 T cells in low levels of IL-2. Journal of leukocyte biology 19 26561569

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