Ask about this productRelated genes to: DPP9 antibody
- Gene:
- DPP9 NIH gene
- Name:
- dipeptidyl peptidase 9
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-21
- Date modifiied:
- 2016-02-08
Related products to: DPP9 antibody
Related articles to: DPP9 antibody
- Over one million patients receive cancer immunotherapy annually, yet the mechanisms underlying life-threatening immune-mediated toxicities remain poorly understood. Checkpoint inhibitor pneumonitis (CIP) is the leading cause of immunotherapy-related mortality, with a case fatality rate approaching 10%, and no genetic risk factors have been described to date. We identified Dipeptidyl-peptidase 9 (DPP9) as the first genetic susceptibility gene for CIP in a clinico-genomics cohort of 4,397 patients treated with immune checkpoint inhibitors. Mechanistically, DPP9 suppresses CARD8 inflammasome activation and IL-18 secretion in human monocytes, a pathway which is engaged prior to CIP onset, with IL-18 selectively elevated in the plasma of patients who subsequently develop CIP. Myeloid-restricted ablation of and in mice recapitulated the pulmonary histopathological and immunological hallmarks of CIP, including granuloma formation, accumulation of IFNγ-producing T cells and monocyte-derived macrophages. Each of these phenotypes were driven by excessive IL-18 secretion. Together, these findings establish DPP9 as a genetic determinant of CIP and nominate IL-18 blockade as a mechanistically rational therapeutic strategy. - Source: PubMed
Publication date: 2026/07/02
Brewer J RichardHan AilinNassar Amin HFarhat Elias BouBlackburn Holly NXiao TianliMirza HarisMowel Walter KSefik EsenHartner SaskiaChiorazzi MichaelIto TakeshiOh Min-HeeMadden Matthew ZRangavajhula AthreyaAdib ElioSaleh Mustafa JMachaalani MarcRakaee MehrdadTafavvoghi MasoudQuattropani ClaireGazetos NicoleGerber DavidFattah FarjanaSoRelle Jeffrey AChoo Dominicvon Itzstein Mitchell SBevans-Fonti ShannonGhanbar MohammadSuresh KarthikMazumder ThomasYe Chun JChoueiri Toni KGusev AlexanderFlavell Richard A - Loss of function mutation in the human gene causes Hatipoglu syndrome leading to severe inflammasomopathy. A key feature of the disease is pancytopenia and patients require bone marrow transplantation, but the mechanism of cell loss is unclear since mutant mice have normal hematopoiesis, suggesting that a distinct mechanism of disease occurs in humans. Here, we present a model of human DPP9 deficiency leveraging reverse genetics in the MISTRG6 humanized mice. We found that CRISPR editing of human CD34 hematopoietic stem and progenitor cells (HSPCs) led to very efficient and persistent gene deletion in vivo. Human deletion recapitulated cytopenia in peripheral blood and in the bone marrow, and cell loss was cell intrinsic. However, deletion led to little transcriptional changes suggesting post-transcriptional regulation in human HSPCs. Mechanistically, DPP9 deficiency led to the activation of the CARD8 inflammasome resulting in HSPC pyroptosis, whereas NLRP1 was dispensable for cell death. Thus, our results reveal a unique human mechanism of disease and offer therapeutic insight for this inflammasomopathy. - Source: PubMed
Publication date: 2026/06/30
Xiao TianliBrewer J RichardCarlino MaximilianHan AilinTakabe YamatoLee Chia-YiZhang FengruiChen MiBlackburn Holly NicoleNassar Amin HWang QiankunBrennad KristenShan LiangSefik EsenKrause Diane SFlavell Richard A - Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL was independently predicted by baseline LTL (p = 0.0004) and treatment duration (p = 0.0056). Longitudinally, ΔLTL increased in nintedanib- versus pirfenidone-treated patients (p = 0.0402) and with treatment duration (p = 0.0233). DNAmAge modestly increased with chronological aging across all clocks, while AgeAcc remained stable, decreasing at follow-up (p = 0.0435) and higher in males (p = 0.0204). Genetic analyses on 17 IPF-associated SNPs confirmed enrichment of established risk variants, including MUC5B and DPP9, and identified an association between higher genetic burden and lower forced vital capacity (p = 0.0136). Extending this approach, genome-wide imputation enabled polygenic risk score (PRS) analysis, revealing significant case-control differences and discrimination (AUC up to 0.79), supporting a measurable polygenic contribution to disease susceptibility. These findings highlight the added value of integrating telomeric, epigenetic, and genome-wide genetic burden-captured through PRS-for improved risk stratification in IPF. - Source: PubMed
Publication date: 2026/07/03
Campisi ManuelaCannella LuanaLiviero FilippoTamiazzo FedericoBalestro ElisabettaSpagnolo PaoloPavanello Sofia - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS). - Source: PubMed
Publication date: 2026/07/02
Farah GaëlleTorres MagaliHenches LeoAschard HuguesGhosn JadeDuval Xavier Rihet PascalSpicuglia SalvatoreMarquet Sandrine - Breast cancer is a heterogenous disease with various molecular subtypes. Among these, triple-negative breast cancer has the worst prognosis due to its high aggressiveness and limited availability of targeted therapies. In breast cancers, reduced expression of dipeptidyl peptidase 9 (DPP9) is associated with a poor patient prognosis. To model reduced DPP9 expression, we transplanted the human triple-negative breast cancer cell line MDA.MB.231 with an inducible genetic DPP9 deficiency in the mammary fat pad of immunocompromised mice. As expected, tumors with DPP9 deficiency showed an increased weight as well as more lung metastasis compared to controls. This phenotype seems to be promoted by increased vessel formation in the tumor due to DPP9 deficiency. Upon irradiation (2 × 9 Gy), tumor growth was initially reduced independent of DPP9 expression, although DPP9-deficient tumors grew out faster after irradiation compared to controls. Additionally, more metastases were formed in mice with DPP9-deficient tumors compared to controls as well as untreated mice with tumors of both genotypes. As proteolytic cleavage of BRCA2 by DPP9 was previously shown to promote repair of DNA double-strand breaks by homologous recombination, the poly-ADP-ribose-polymerase (PARP) inhibitor Olaparib (25 mg/kg) was applied to mice in combination with local irradiation in order to test for synthetic lethality effects. The results revealed further reduction in tumor growth compared to untreated and irradiated mice. Furthermore, DPP9 deficiency together with combined irradiation/PARP inhibition further reduced tumor growth compared to control tumors. Yet, metastasis formation presented with a mixed outcome in mice with DPP9-deficient tumors. In summary, reduced DPP9 levels enhanced primary tumor growth but sensitized triple-negative breast tumors to a combination of irradiation and Olaparib. - Source: PubMed
Publication date: 2026/06/10
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