Degranulation of human cytotoxic lymphocytes is a major source of proteolytically active soluble CD26/DPP4.
CD26
Dipeptidylpeptidase 4
Lymphocyte-mediated cytotoxicity
NK cells
Secretory granules
T cells
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
12
02
2019
accepted:
24
06
2019
revised:
14
06
2019
pubmed:
14
7
2019
medline:
7
3
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease detected on several immune cells and on epithelial cells of various organs. Besides the membrane-bound enzyme, a catalytically active soluble form (sCD26/DPP4) is detected in several body fluids. Both variants cleave off dipeptides from the N-termini of various chemokines, neuropeptides, and hormones. CD26/DPP4 plays a fundamental role in the regulation of blood glucose levels by inactivating insulinotropic incretins and CD26/DPP4 inhibitors are thus routinely used in diabetes mellitus type 2 therapy to improve glucose tolerance. Such inhibitors might also prevent the CD26/DPP4-mediated inactivation of the T-cell chemoattractant CXCL10 released by certain tumors and thus improve anti-tumor immunity and immunotherapy. Despite its implication in the regulation of many (patho-)physiological processes and its consideration as a biomarker and therapeutic target, the cellular source of sCD26/DPP4 remains highly debated and mechanisms of its release are so far unknown. In line with recent reports that activated T lymphocytes could be a major source of sCD26/DPP4, we now demonstrate that CD26/DPP4 is stored in secretory granules of several major human cytotoxic lymphocyte populations and co-localizes with effector proteins such as granzymes, perforin, and granulysin. Upon stimulation, vesicular CD26/DPP4 is rapidly translocated to the cell surface in a Ca
Identifiants
pubmed: 31300870
doi: 10.1007/s00018-019-03207-0
pii: 10.1007/s00018-019-03207-0
doi:
Substances chimiques
DPP4 protein, human
EC 3.4.14.5
Dipeptidyl Peptidase 4
EC 3.4.14.5
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
751-764Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : JA 610 7/1
Organisme : Deutsche Forschungsgemeinschaft
ID : Ka 502/19-1
Organisme : Deutsche Forschungsgemeinschaft
ID : Cluster of Excellence Exc 306
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