Affinage

DPP4

Dipeptidyl peptidase 4 · UniProt P27487

Length
766 aa
Mass
88.3 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 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

DPP4/CD26 is a type II transmembrane serine exopeptidase that cleaves N-terminal X-Pro/X-Ala dipeptides from regulatory peptides—including the incretins GLP-1, GLP-2 and GIP, neuropeptides, and chemokines such as RANTES/CCL5, SDF-1/CXCL12 and eotaxin/CCL11—thereby inactivating or modulating their bioactivity (PMID:10588446). Both its peptidase activity and the dimerization required for it depend on the C-terminal portion of its alpha/beta hydrolase domain, which is also needed for normal cell-surface expression (PMID:12534281). Beyond catalysis, DPP4 acts as a multifunctional cell-surface scaffold: it binds adenosine deaminase (ADA) and CD45 in its extracellular domain to co-stimulate T cells through the CD3 pathway, and the ADA interaction can bridge T cells to dendritic cells via a CD26–ADA–A2AR trimer (PMID:9683260, PMID:9553764, PMID:29497379). It associates with and co-internalizes alongside the chemokine receptor CXCR4 upon SDF-1α stimulation, and engages caveolin-1 to trigger NF-κB activation and CD86 upregulation on antigen-presenting cells, driving antigen-specific T-cell responses (PMID:11278278, PMID:16622717). Through these enzymatic and scaffolding activities DPP4 shapes immune cell adhesion, motility and cytokine output—mediating ADA-dependent T-cell adhesion via LFA-1, restraining T-cell migration through chemokine processing, and promoting IL-10-producing regulatory phenotypes (PMID:11772392, PMID:19687096, PMID:25548232). In disease contexts, DPP4 is the receptor for the MERS-CoV spike receptor-binding domain, which contacts blades IV and V of its β-propeller (PMID:23831647), and its subcellular localization governs ferroptosis: TP53 non-transcriptionally suppresses plasma-membrane DPP4 to limit DPP4-driven lipid peroxidation (PMID:28813679). DPP4 also links metabolism and inflammation, with hepatocyte-secreted DPP4 acting with factor Xa through caveolin-1/PAR2 to activate adipose macrophages and promote insulin resistance (PMID:29562231), and contributes to fibrosis, cancer invasion/angiogenesis, and the senescent-cell secretory program (PMID:34808238, PMID:35163100, PMID:37097759).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Established DPP4 as a serine exopeptidase whose physiological role is the inactivation of a broad set of regulatory peptides via X-Pro/X-Ala cleavage, defining its core biochemical identity.

    Evidence In vitro enzymatic assays and in vivo peptide cleavage across multiple substrates (GLP-1, GIP, RANTES, SDF-1, eotaxin, etc.)

    PMID:10588446

    Open questions at the time
    • Does not establish in vivo substrate hierarchy or which cleavages dominate in specific tissues
    • No structural basis for substrate selectivity
  2. 1998 Medium

    Showed that DPP4 has a non-enzymatic co-stimulatory function, mapping the T-cell co-stimulation epitopes and the ADA/CD45 binding interactions distinct from catalysis.

    Evidence Epitope mapping with truncated/chimeric mutants, cross-blocking mAbs, cell-surface binding and co-IP, T-cell activation assays

    PMID:9553764 PMID:9683260

    Open questions at the time
    • Mechanism coupling ADA/CD45 binding to intracellular signaling not resolved
    • Single-lab epitope mapping
  3. 2001 High

    Linked DPP4 to chemokine receptor biology and HIV, showing co-internalization with CXCR4 and gp120 binding at a site distinct from ADA.

    Evidence Reciprocal co-IP, co-internalization with CXCR4 mutants, pertussis toxin treatment, gp120 competition

    PMID:11278278

    Open questions at the time
    • Functional consequence of CXCR4 co-internalization for chemotaxis not defined
    • Single lab
  4. 2002 Medium

    Demonstrated that the CD26–ADA interaction is a functional adhesion mechanism, coupling surface ADA capture to LFA-1-mediated T-cell adhesion.

    Evidence Cell adhesion assays with ADA-expressing Caco-2 cells, anti-CD26/ADA-site blocking, integrin activation FACS

    PMID:11772392

    Open questions at the time
    • Signaling pathway from CD26 to LFA-1 activation not delineated
    • ~50% effect size, single lab
  5. 2003 High

    Resolved the structural requirement for activity, showing dimerization and peptidase function both require the C-terminal hydrolase domain region.

    Evidence Domain-swap chimeras (DP8/DP9), cell-surface expression and enzymatic assays

    PMID:12534281

    Open questions at the time
    • No crystal structure of the catalytic domain in this study
    • Does not address scaffolding-domain folding requirements
  6. 2006 Medium

    Identified caveolin-1 as a CD26 partner on APCs and traced a CD26→caveolin-1 phosphorylation→NF-κB→CD86 signaling cascade driving T-cell activation.

    Evidence Co-precipitation, site-directed mutagenesis (residues 201–211, Ser630), caveolin-1 siRNA, NF-κB reporter, CD86 and proliferation assays

    PMID:16622717

    Open questions at the time
    • Role of catalytic Ser630 in a binding interaction unexplained mechanistically
    • Single lab
  7. 2009 Medium

    Showed DPP4 restrains T-cell motility through chemokine processing, with CD26-processed CXCL12/CCL5 inducing TSP-1 and CD91/LRP.

    Evidence CD26 siRNA, antibody modulation, migration assays, flow cytometry for TSP-1/CD91

    PMID:19687096

    Open questions at the time
    • Direct enzymatic vs scaffold contribution to TSP-1 induction not separated
    • Single lab
  8. 2011 Medium

    Established in vivo that CD26 protectively restricts allergic airway inflammation, consistent with its chemokine-inactivating activity.

    Evidence CD26-knockout mice, OVA sensitization, BAL cytokine/chemokine measurement, eosinophil quantification

    PMID:22101691

    Open questions at the time
    • Does not isolate which substrate cleavages (eotaxin/RANTES) drive the phenotype
    • Single model
  9. 2011 Medium

    Defined transcriptional control of CD26 in colon cancer, with c-Myc repressing and Cdx2 enhancing expression in a confluence-dependent manner.

    Evidence c-Myc overexpression and siRNA, Cdx2 siRNA, qPCR, western blot, immunofluorescence

    PMID:21284881

    Open questions at the time
    • Direct promoter binding by these factors not shown
    • HIF-1α requirement mechanism unresolved
  10. 2013 High

    Defined DPP4 as the MERS-CoV receptor at atomic resolution, mapping the spike RBD to specific β-propeller blades.

    Evidence X-ray crystallography of RBD–DPP4 complex, SPR (Kd = 16.7 nM)

    PMID:23831647

    Open questions at the time
    • Does not address how receptor engagement relates to peptidase activity or species tropism determinants in vivo
  11. 2014 Medium

    Extended DPP4 scaffolding to cancer invasion, showing CD26–α5β1 integrin complexes drive FAK/Cas-L signaling and CD9 negatively regulates this axis.

    Evidence Reciprocal co-IP, CD26/CD9 siRNA, gene transfer, invasion assays, FAK/Cas-L western blots in mesothelioma

    PMID:24466195

    Open questions at the time
    • Whether catalytic activity is required for the integrin interaction unknown
    • Single cancer type
  12. 2014 Medium

    Connected CD26 to two additional cellular programs—IL-10-skewed regulatory T-cell output (NFAT/ERK/EGR2) and osteoclast differentiation (p38/MKK3-6/MITF).

    Evidence Co-stimulation assays, EGR2 siRNA, pathway inhibitors, anti-CD26 mAb, TRAP/bone resorption assays

    PMID:24821427 PMID:25548232

    Open questions at the time
    • Upstream receptor coupling of CD26 to these MAPK/NFAT cascades not defined
    • Single-lab readouts
  13. 2017 High

    Revealed that DPP4 subcellular localization is a ferroptosis switch controlled non-transcriptionally by TP53, with plasma-membrane DPP4 driving lipid peroxidation.

    Evidence TP53 KO, subcellular fractionation, DPP4 activity and lipid peroxidation assays, ferroptosis readouts

    PMID:28813679

    Open questions at the time
    • Molecular mechanism by which membrane DPP4 promotes lipid peroxidation not detailed
    • Direct TP53–DPP4 contact not structurally defined
  14. 2018 High

    Positioned secreted hepatocyte DPP4 as a metabolic inflammatory signal acting through caveolin-1/factor Xa/PAR2 on adipose macrophages to cause insulin resistance.

    Evidence Hepatocyte-specific DPP4 silencing in vivo, ATM caveolin-1/PAR2 siRNA, insulin resistance and inflammation measurements

    PMID:29562231

    Open questions at the time
    • Whether DPP4 peptidase activity is required for PAR2 pathway activation not isolated
    • Human relevance not established
  15. 2018 Medium

    Showed ADA can physically bridge CD26 on T cells to A2AR on dendritic cells, defining an intercellular signaling triad.

    Evidence Inter-cellular NanoBRET, ADA mutagenesis, dynamic mass redistribution, ligand binding

    PMID:29497379

    Open questions at the time
    • Functional immune consequence of the trimer not demonstrated
    • Single lab biophysical assays
  16. 2022 Medium

    Linked CD26 to colorectal cancer angiogenesis/metastasis through a CAV1/MMP1 axis, with CAV1 epistatically suppressing CD26-driven MMP1.

    Evidence CD26 overexpression/knockdown, genome-wide array, qPCR, migration/invasion, in vivo model, CAV1 rescue

    PMID:35163100

    Open questions at the time
    • Mechanism by which CD26 induces MMP1 not defined
    • Single lab
  17. 2020 High

    Identified glucocorticoid receptor as a direct transcriptional inducer of DPP4 via promoter GREs, coupling steroid signaling to macrophage migration.

    Evidence GR ChIP/GRE mapping, GR and DPP4 siRNA, RU-486, migration and activity assays

    PMID:31988243

    Open questions at the time
    • Whether enzymatic or scaffold DPP4 function drives migration not separated
  18. 2023 Medium

    Implicated DPP4 in senescence biology—as a surface 'uptake repressor' on senescence-associated EVs and as a driver of a complement/coagulation SASP whose inhibition is senomorphic/senolytic.

    Evidence EV surfaceome MS, ectopic DPP4 overexpression and uptake assays; DPP4 silencing/inhibition, conditioned-media proteomics, single-cell VSMC analysis, murine atherosclerosis

    PMID:37097759 PMID:37862381

    Open questions at the time
    • Molecular mechanism of EV uptake repression by DPP4 unknown
    • Causal SASP substrate of DPP4 in VSMCs not identified
  19. 2019 Medium

    Demonstrated that DPP4 truncation of CCL11 limits anti-tumor eosinophil recruitment, providing a substrate-level rationale for DPP4 inhibition in cancer immunity.

    Evidence Sitagliptin in tumor models, eosinophil depletion, IL-33-dependence epistasis, chemokine measurement

    PMID:30778250

    Open questions at the time
    • Contribution of other DPP4 substrates to the phenotype not excluded
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DPP4 partitions between its catalytic and scaffolding functions across contexts, and which molecular features dictate its localization (membrane vs nucleus vs EV vs secreted) and partner selection in a given cell type.
  • No unified model linking localization control to functional output
  • Enzymatic vs non-enzymatic contributions not systematically dissected in most disease settings
  • No structure of full-length DPP4 bound to its scaffolding partners

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 1 GO:0005634 nucleus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ADACAV1CD45CD9CXCR4F2RL1ITGA5TP53
Complex memberships
CD26-ADA-A2AR trimerCD26-CXCR4 complexCD26-α5β1 integrin complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 DPP4/CD26 functions as a serine exopeptidase that cleaves N-terminal dipeptides from regulatory peptides bearing L-proline or L-alanine at the penultimate position, thereby inactivating substrates including GLP-1, GLP-2, GIP, NPY, peptide YY, GHRH, RANTES, SDF-1, eotaxin, and MDC; this activity was demonstrated through in vitro and in vivo experiments. In vitro enzymatic assays and in vivo peptide cleavage experiments Regulatory peptides High 10588446
2003 CD26/DPP4 dimerization and peptidase activity both require the C-terminal portion of the predicted alpha/beta hydrolase domain (residues 501–766); chimeric proteins replacing this region with homologous sequences from DP8 or DP9 lacked dimerization and peptidase activity. Deletion of N-terminal residues of the alpha/beta hydrolase domain also ablated peptidase activity and greatly reduced cell-surface expression. Domain-swap chimera mutagenesis, cell-surface expression assay, enzymatic activity assay Biochemistry High 12534281
1998 CD26 co-stimulates T-cell activation through the CD3 pathway; the epitopes required for T-cell co-stimulation were mapped to the 248–358 and 359–449 amino acid regions, while the ADA binding domain lies within the 359–449 region, using truncated and human-rat swap mutants plus cross-blocking with 13 anti-CD26 mAbs. Epitope mapping with truncated/chimeric CD26 mutants, cross-blocking assays, T-cell co-stimulation functional assays Molecular immunology Medium 9683260
1998 CD26 on the surface of T cells acts as the receptor for adenosine deaminase (ADA), binding ADA on the cell surface and thereby mediating co-stimulatory signals; CD26 also interacts with CD45, a protein tyrosine phosphatase, in its extracellular domain. Cell-surface binding assays, co-immunoprecipitation, functional T-cell activation assays Immunological reviews Medium 9553764
2001 CD26 co-distributes and co-immunoprecipitates with CXCR4 in T and B cell lines; upon SDF-1α stimulation, CD26 is co-internalized with CXCR4 through a process requiring CXCR4 internalization capacity but not pertussis-toxin-sensitive G-protein signaling. HIV-1 gp120 interacts with CD26 and disrupts ADA/CD26 interaction by binding a site distinct from the ADA-binding domain. Co-immunoprecipitation, co-internalization assays with CXCR4 mutants, pertussis toxin treatment, gp120 competition assays The Journal of biological chemistry High 11278278
2002 CD26-ADA interaction on the lymphocyte surface mediates T-cell adhesion to epithelial cells: CD26 overexpression increased T-cell adhesion to ADA-expressing Caco-2 cells by ~50%, and this was blocked by anti-CD26 antibody targeting the ADA-binding site or by exogenous ADA; adhesion was mediated through LFA-1 integrin activation. Cell adhesion assays, anti-CD26 antibody blocking, exogenous ADA competition, integrin activation FACS The Biochemical journal Medium 11772392
2013 Crystal structures of the free MERS-CoV spike receptor-binding domain (RBD) and its complex with CD26/DPP4 revealed that the viral RBD binds blades IV and V of the CD26 β-propeller via hydrophilic contacts; binding affinity was measured at Kd = 16.7 nM by surface plasmon resonance. X-ray crystallography, surface plasmon resonance Nature High 23831647
2017 TP53 limits erastin-induced ferroptosis by directly blocking DPP4 activity in a transcription-independent manner; loss of TP53 allows DPP4 to accumulate at the plasma membrane where it drives lipid peroxidation and ferroptosis, while nuclear DPP4 (promoted by TP53) is inactive in this pathway. Loss-of-function (TP53 knockout), subcellular fractionation, DPP4 activity assay, lipid peroxidation measurement, ferroptosis assay Cell reports High 28813679
2006 CD26 binds caveolin-1 on antigen-presenting cells (APCs) via residues 201–211 and the catalytic serine at position 630 of CD26; CD26–caveolin-1 interaction leads to caveolin-1 phosphorylation on APCs, NF-κB activation, and upregulation of CD86, thereby driving antigen-specific T-cell activation. Co-precipitation, site-directed mutagenesis of CD26, siRNA knockdown of caveolin-1, NF-κB reporter, CD86 upregulation assay, T-cell proliferation assay Modern rheumatology Medium 16622717
2009 CD26 acts as an endogenous inhibitor of T-cell motility: CD26-processed chemokines CXCL12 and CCL5 induce thrombospondin-1 (TSP-1) surface expression on T lymphocytes through a CD26-controlled mechanism; TSP-1 then stimulates CD91/LRP expression. siRNA silencing or antibody-induced modulation of CD26 enhanced TSP-1 expression and increased T-cell migration. siRNA knockdown of CD26, antibody-induced CD26 modulation, cell migration assay, flow cytometry for TSP-1 and CD91 Journal of immunology Medium 19687096
2014 CD26 co-precipitates with and inversely regulates CD9 in malignant mesothelioma cells; CD26 also co-precipitates with α5β1 integrin and potentiates tumor cell invasion through this interaction. CD9 negatively regulates CD26 expression and reduces the CD26–α5β1 integrin complex, suppressing FAK and Cas-L phosphorylation. Co-immunoprecipitation, siRNA knockdown of CD26 and CD9, gene transfer, cell invasion assay, western blotting of FAK/Cas-L phosphorylation PloS one Medium 24466195
2018 Obesity-induced hepatocyte DPP4 is secreted and acts together with plasma factor Xa to activate adipose tissue macrophages (ATMs) via caveolin-1 on ATMs and PAR2 signaling; silencing hepatocyte DPP4 suppressed VAT inflammation and insulin resistance in mice, while silencing ATM caveolin-1 or PAR2 produced a similar effect. Hepatocyte-specific DPP4 silencing (in vivo), caveolin-1 and PAR2 siRNA in ATMs, insulin resistance measurement, adipose tissue inflammation quantification Nature High 29562231
2018 ADA can form a trimeric CD26–ADA–A2AR complex bridging T cells (expressing CD26) and dendritic cells (expressing A2AR); this was demonstrated by NanoBRET and site-directed mutagenesis of ADA residues at the A2AR binding interface. NanoBRET inter-cellular BRET, site-directed mutagenesis of ADA, dynamic mass redistribution assay, ligand binding Frontiers in pharmacology Medium 29497379
2014 CD26 co-stimulation of CD3 and CD26 induces preferential IL-10 production in CD4+ T cells via NFAT and Raf-MEK-ERK pathways; EGR2 is induced via NFAT and AP-1 signaling and is required for IL-10 production (EGR2 knockdown reduced IL-10). CD3/CD26-stimulated T cells suppress bystander T-cell proliferation in an IL-10-dependent manner. Co-stimulation assays, EGR2 siRNA knockdown, pathway inhibitors (NFAT, ERK), IL-10 ELISA, suppression assay Journal of immunology Medium 25548232
2014 CD26 signaling during osteoclastogenesis promotes p38 MAPK and MKK3/6 phosphorylation leading to MITF phosphorylation, driving osteoclast differentiation. Anti-CD26 humanized monoclonal antibody blocked early OC differentiation by inactivating this pathway and impaired bone resorption. Anti-CD26 mAb treatment, western blotting (p38 MAPK, MKK3/6, MITF phosphorylation), TRAP/multinucleated OC counting, bone resorption assay Journal of bone and mineral research Medium 24821427
2020 Glucocorticoids directly induce DPP4 gene expression in macrophages via glucocorticoid receptor (GR) binding to two glucocorticoid response elements (GREs) in the DPP4 promoter; this GR-induced DPP4 expression mediates glucocorticoid-induced macrophage migration, as demonstrated by GR siRNA and DPP4 siRNA knockdown blocking dexamethasone-induced migration. GR ChIP (GRE identification), GR and DPP4 siRNA knockdown, GR antagonist (RU-486), macrophage migration assay, DPP4 enzymatic activity assay The Journal of biological chemistry High 31988243
2021 DPP4 is a Wnt/β-catenin-responsive gene and a functional mediator of fibrotic dermal remodeling: genetic inducible Wnt activation caused dermal fibrosis with ECM expansion and adipocyte loss, and genetic evidence showed the Wnt/DPP4 axis is required for this fibrotic transformation; DPP4 inhibitors reversed established Wnt-induced fibrosis. Genetically inducible Wnt activation mouse model, DPP4 genetic loss-of-function, Wnt/β-catenin reporter, histology, DPP4 inhibitor treatment The Journal of investigative dermatology Medium 34808238
2011 CD26-deficient mice show enhanced ovalbumin-induced airway inflammation with increased Th2 cytokines (IL-4, IL-5, IL-13), elevated eotaxin and RANTES chemokines and their receptors (CCR3, CCR5), and increased pulmonary eosinophil infiltration, establishing a protective/regulatory role for CD26 in restricting allergic airway inflammation. CD26 gene-knockout mouse model, OVA sensitization/challenge, cytokine mRNA and protein measurement (BAL fluid), flow cytometry, immunohistology European journal of immunology Medium 22101691
2023 DPP4 on the surface of senescence-associated extracellular vesicles (S-EVs) prevents their uptake by proliferating cells; ectopic overexpression of DPP4 in HeLa cells produced EVs that were no longer taken up by other proliferating cells, identifying DPP4 as an 'uptake repressor' on S-EVs. Surfaceome mass spectrometry of EVs, ectopic DPP4 overexpression in EV-producing cells, EV uptake assay Proceedings of the National Academy of Sciences Medium 37862381
2022 CD26 induces colorectal cancer angiogenesis and metastasis through a CAV1/MMP1 signaling axis: CD26 overexpression upregulated MMP1 (identified by genome-wide mRNA array), and overexpression of CAV1 abrogated CD26-regulated MMP1 induction in CRC cell lines. CD26 overexpression/knockdown, genome-wide mRNA expression array, qPCR, cell migration/invasion assay, in vivo mouse model, CAV1 overexpression epistasis experiment International journal of molecular sciences Medium 35163100
2023 DPP4 inhibition in senescent vascular smooth muscle cells (VSMCs) reduced a unique SASP signature enriched in complement and coagulation factors, reduced senescent cell burden, and improved atherosclerotic plaque stability in mice; single-cell analysis confirmed senomorphic and senolytic effects of DPP4 inhibition. DPP4 silencing and inhibition, conditioned media proteomics, single-cell resolution VSMC analysis, murine atherosclerosis model The Journal of clinical investigation Medium 37097759
2011 In colon cancer cell lines, CD26 expression is regulated at the transcriptional level in a confluence-dependent manner: c-Myc acts as a repressor (ectopic c-Myc decreased CD26; c-Myc siRNA increased it), while Cdx2 acts as an enhancer (Cdx2 siRNA decreased CD26). HIF-1α was required but not sufficient for CD26 upregulation under serum depletion. Transient transfection of c-Myc expression plasmid, c-Myc siRNA, Cdx2 siRNA, real-time PCR, western blotting, immunofluorescence BMC cancer Medium 21284881
2019 DPP4 post-translationally truncates CCL11, reducing eosinophil recruitment to tumors; inhibition of DPP4 by sitagliptin increased CCL11 levels and eosinophil infiltration into solid tumors, with tumor control dependent on eosinophils and IL-33 tumor-cell expression. DPP4 inhibitor (sitagliptin) in pre-clinical tumor models, eosinophil depletion, degranulation inhibitors, lymphocyte-deficient mice, chemokine measurement Nature immunology Medium 30778250

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides. Regulatory peptides 1049 10588446
2017 The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity. Cell reports 786 28813679
2013 Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 557 23831647
1998 The structure and function of CD26 in the T-cell immune response. Immunological reviews 363 9553764
2016 Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clinical and experimental immunology 346 26919392
2015 DPP4 in Diabetes. Frontiers in immunology 328 26284071
2001 CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scandinavian journal of immunology 312 11555388
1994 CD26: a surface protease involved in T-cell activation. Immunology today 311 7911022
2017 SFRP2/DPP4 and FMO1/LSP1 Define Major Fibroblast Populations in Human Skin. The Journal of investigative dermatology 278 29080679
2003 The multifunctional or moonlighting protein CD26/DPPIV. European journal of cell biology 267 12647932
2019 Clinical Use of DPP-4 Inhibitors. Frontiers in endocrinology 243 31275246
2018 Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature 230 29562231
2017 Identification of senescent cell surface targetable protein DPP4. Genes & development 207 28877934
2008 Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends in immunology 205 18456553
2019 Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nature immunology 171 30778250
2009 On the origin of serum CD26 and its altered concentration in cancer patients. Cancer immunology, immunotherapy : CII 170 19557413
2015 DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circulation research 165 25858071
2009 Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme. Current medicinal chemistry 164 19689275
2008 The role of CD26/dipeptidyl peptidase IV in cancer. Frontiers in bioscience : a journal and virtual library 164 17981655
2020 Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19. Acta diabetologica 157 32506195
2005 Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 142 15939342
2019 CD26/DPP4 - a potential biomarker and target for cancer therapy. Pharmacology & therapeutics 132 30822465
2023 Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target. Science (New York, N.Y.) 123 37535747
2020 COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity? Journal of diabetes 117 32394639
2015 High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells. Immunology 113 25752900
2013 CD26/DPP4 levels in peripheral blood and T cells in patients with type 2 diabetes mellitus. The Journal of clinical endocrinology and metabolism 98 23539735
2004 CD26/dipeptidyl peptidase IV and its role in cancer. Histology and histopathology 91 15375776
2016 Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins. Clinical and experimental immunology 90 26671446
2001 Comodulation of CXCR4 and CD26 in human lymphocytes. The Journal of biological chemistry 86 11278278
2023 CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer. Nature communications 81 36635273
2020 DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications? Frontiers in pharmacology 78 32848769
2011 Incretin effect: GLP-1, GIP, DPP4. Diabetes research and clinical practice 78 21864749
2019 DPP-4 Inhibition and the Path to Clinical Proof. Frontiers in endocrinology 74 31275243
2000 Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clinical and experimental rheumatology 70 10949720
2020 Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans. Nature communications 65 32724076
2018 Significance of circulatory DPP4 activity in metabolic diseases. IUBMB life 65 29331088
1997 Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology 65 9413751
2015 Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice. Clinical & experimental metastasis 63 26233333
2003 Structural requirements for catalysis, expression, and dimerization in the CD26/DPIV gene family. Biochemistry 61 12534281
2016 Hepatic DPP4 DNA Methylation Associates With Fatty Liver. Diabetes 57 27999105
2002 Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. The Biochemical journal 57 11772392
2018 Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins. Frontiers in pharmacology 56 29497379
2011 Higher serum DPP-4 enzyme activity and decreased lymphocyte CD26 expression in type 1 diabetes. Pathology oncology research : POR 50 21785903
2014 DPPIV (CD26) as a novel stem cell marker in Ph+ chronic myeloid leukaemia. European journal of clinical investigation 49 25371066
2014 DPP-4 inhibitors: focus on safety. Expert opinion on drug safety 49 25488788
2008 DPP4 inhibitors for diabetes--what next? Biochemical pharmacology 47 18755155
1995 CD26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma. Laboratory investigation; a journal of technical methods and pathology 46 7474942
2016 DPPIV/CD26: a tumor suppressor or a marker of malignancy? Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 45 26943912
2015 CD26 a cancer stem cell marker and therapeutic target. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 44 25960228
2014 DPP-4 inhibitors: pharmacological differences and their clinical implications. Expert opinion on drug safety 44 25171159
2022 CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling. International journal of molecular sciences 42 35163100
2019 Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways. EBioMedicine 42 30738832
2017 Expansion of CD26 positive fibroblast population promotes keloid progression. Experimental cell research 42 28454879
2021 DPP4 Activity, Hyperinsulinemia, and Atherosclerosis. The Journal of clinical endocrinology and metabolism 41 33570554
2019 The CD26/DPP4-inhibitor vildagliptin suppresses lung cancer growth via macrophage-mediated NK cell activity. Carcinogenesis 41 30698677
2018 LncRNA-OIS1 regulates DPP4 activation to modulate senescence induced by RAS. Nucleic acids research 41 29481642
2002 CD26: an expanding role in immune regulation and cancer. Histology and histopathology 39 12371149
2009 A CD26-controlled cell surface cascade for regulation of T cell motility and chemokine signals. Journal of immunology (Baltimore, Md. : 1950) 38 19687096
2006 T-cell activation via CD26 and caveolin-1 in rheumatoid synovium. Modern rheumatology 38 16622717
2023 DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice. The Journal of clinical investigation 37 37097759
2020 CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway. Burns & trauma 37 33150188
2013 Low DPP4 expression and activity in multiple sclerosis. Clinical immunology (Orlando, Fla.) 37 24412911
2022 Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology. Biomedicines 36 36009573
2015 CD26 costimulatory blockade improves lung allograft rejection and is associated with enhanced interleukin-10 expression. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 36 26755203
2015 Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells. PloS one 35 26222679
2021 Skin Fibrosis and Recovery Is Dependent on Wnt Activation via DPP4. The Journal of investigative dermatology 34 34808238
2020 The protective role of DPP4 inhibitors in atherosclerosis. European journal of pharmacology 34 32097656
2022 DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits. Military Medical Research 33 35986429
2019 CD26 and Asthma: a Comprehensive Review. Clinical reviews in allergy & immunology 33 27561663
2008 CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation. Frontiers in bioscience : a journal and virtual library 33 17981668
2022 Dipeptidyl Peptidase 4 (DPP4) as A Novel Adipokine: Role in Metabolism and Fat Homeostasis. Biomedicines 32 36140405
2020 DPP-4 inhibition and COVID-19: From initial concerns to recent expectations. Diabetes & metabolism 31 33249199
2000 Good or evil: CD26 and HIV infection. Journal of dermatological science 31 10698152
1998 Correlation of the epitopes defined by anti-CD26 mAbs and CD26 function. Molecular immunology 31 9683260
2020 Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. The Journal of biological chemistry 30 31988243
2018 A novel role for CD26/dipeptidyl peptidase IV as a therapeutic target. Frontiers in bioscience (Landmark edition) 30 29772527
2016 Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells. Allergy 30 27091730
2014 CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells. PloS one 30 24466195
2021 Renoprotective Effects of DPP-4 Inhibitors. Antioxidants (Basel, Switzerland) 29 33562528
2023 Surfaceome analysis of extracellular vesicles from senescent cells uncovers uptake repressor DPP4. Proceedings of the National Academy of Sciences of the United States of America 28 37862381
2014 Blockade of CD26 signaling inhibits human osteoclast development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 28 24821427
2022 CD26/DPP4 as a Therapeutic Target in Nonalcoholic Steatohepatitis Associated Hepatocellular Carcinoma. Cancers 26 35053615
2022 Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis. British journal of pharmacology 26 36196001
2017 Regulation and roles of CD26/DPPIV in hematopoiesis and diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 28448874
2016 Boning up on DPP4, DPP4 substrates, and DPP4-adipokine interactions: Logical reasoning and known facts about bone related effects of DPP4 inhibitors. Bone 26 27535784
2011 Enhanced ovalbumin-induced airway inflammation in CD26-/- mice. European journal of immunology 25 22101691
2024 Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity. Cell reports. Medicine 24 38688275
2020 A novel chimeric antigen receptor redirecting T-cell specificity towards CD26+ cancer cells. Leukemia 23 32317776
2020 SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons? Diabetes research and clinical practice 23 32335097
2013 Expression of CD26 and CXCR4 in prostate carcinoma and its relationship with clinical parameters. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 23 24379839
2023 Association of Dipeptidylpeptidase 4 (CD26) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis. Arthritis & rheumatology (Hoboken, N.J.) 22 36704903
2018 Delayed allogeneic skin graft rejection in CD26-deficient mice. Cellular & molecular immunology 22 29572550
2011 Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines. BMC cancer 22 21284881
2011 Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines. Oncology reports 22 21894438
1995 Antibody-induced modulation of CD26 surface expression. Immunology 22 7790033
2022 Therapeutic Perspectives of CD26 Inhibitors in Imune-Mediated Diseases. Molecules (Basel, Switzerland) 21 35889373
2021 CD26/Dipeptidyl Peptidase IV and Its Multiple Biological Functions. Cureus 21 33777580
2021 Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control. Clinical medicine insights. Endocrinology and diabetes 21 34733107
2018 Anticonvulsant agent DPP4 inhibitor sitagliptin downregulates CXCR3/RAGE pathway on seizure models. Experimental neurology 21 29885296
2014 CD26-mediated induction of EGR2 and IL-10 as potential regulatory mechanism for CD26 costimulatory pathway. Journal of immunology (Baltimore, Md. : 1950) 21 25548232

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