ArticleMolecular metabolism2017
KLK5 induces shedding of DPP4 from circulatory Th17 cells in type 2 diabetes.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.Nature communications · 2020Trial
- Dipeptidyl Peptidase-4 Inhibitor Use and Risk of Pemphigus Vulgaris and Foliaceus: A Retrospective Cohort Study Using Databases of the Korea National Health Insurance Claims and the National Health Screening Examination.The Journal of dermatology · 2026Article
- The role of DPP4 in viral infections: from receptor biology to antiviral target.Archives of virology · 2026Review
- Dual-source DPP4 drives intestinal fibrosis in Crohn's disease: synergistic therapeutic targeting of host and microbiota pathways.Gut microbes · 2025Article
- Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
- Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population.BMJ open diabetes research & care · 2024Article
- Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy.Cancers · 2024Review
- Bidirectional relation between dipeptidyl peptidase 4 and angiotensin II type I receptor signaling.American journal of physiology. Cell physiology · 2024Article
- A Systems Biology Approach Unveils a Critical Role of DPP4 in Upper Gastrointestinal Cancer Patient Outcomes.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2024Article
- Renal cancer secretome induces migration of mesenchymal stromal cells.Stem cell research & therapy · 2023Article
- COVID-19: Diabetes Perspective-Pathophysiology and Management.Pathogens (Basel, Switzerland) · 2023Review
- Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases.International journal of molecular sciences · 2022Article
- Association of the rs17574Diagnostics (Basel, Switzerland) · 2022Article
- A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Article
- Open Chromatin State of Dpp4 With Glucocorticoid Treatment-Setting up Shop for Metasteroid Diabetes?Endocrinology · 2022Article
- Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease.Frontiers in immunology · 2022 · on this mapReview
- Review
- Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer.Diagnostics (Basel, Switzerland) · 2021Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIncreasing plasma levels and activity of dipeptidyl peptidase-4 (DPP4 or CD26) are associated with rapid progression of metabolic syndrome to overt type 2 diabetes mellitus (T2DM). While DPP4 inhibitors are increasingly used as anti-hyperglycemic agents, the reason for the increase in plasma DPP4 activity in T2DM patients remains elusive.
methodsWe looked into the source of plasma DPP4 activity in a cohort of 135 treatment naive nonobese (BMI < 30) T2DM patients. A wide array of ex vivo, in vitro, and in silico methods were employed to study enzyme activity, gene expression, subcellular localization, protease identification, surface expression, and protein-protein interactions.
resultsWe show that circulating immune cells, particularly CD4+ T cells, served as an important source for the increase in plasma DPP4 activity in T2DM. Moreover, we found kallikrein-related peptidase 5 (KLK5) as the enzyme responsible for cleaving DPP4 from the cell surface by directly interacting with the extracellular loop. Expression and secretion of KLK5 is induced in CD4+ T cells of T2DM patients. In addition, KLK5 shed DPP4 from circulating CD4+ T helper (Th)17 cells and shed it into the plasma of T2DM patients. Similar cleavage and shedding activities were not seen in controls.
conclusionsOur study provides mechanistic insights into the molecular interaction between KLK5 and DPP4 as well as CD4+ T cell derived KLK5 mediated enzymatic cleavage of DPP4 from cell surface. Thus, our study uncovers a hitherto unknown cellular source and mechanism behind enhanced plasma DPP4 activity in T2DM.
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