Internal Disulfide Bonding and Glycosylation of Interleukin-7 Protect Against Proteolytic Inactivation by Neutrophil Metalloproteinases and Serine Proteases.
Cell Line
Cell Line, Tumor
Cytokines
/ metabolism
Glycosylation
Humans
Inflammation
/ metabolism
Interleukin-7
/ metabolism
Leukocytes, Mononuclear
/ metabolism
Matrix Metalloproteinase 9
/ metabolism
Neutrophil Activation
/ physiology
Neutrophils
/ metabolism
Proteolysis
Serine Proteases
/ metabolism
IL-7
matrix metalloproteinase-9
neutrophils
proliferation
proteolysis
signal transduction
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
04
2021
accepted:
14
06
2021
entrez:
19
7
2021
pubmed:
20
7
2021
medline:
22
12
2021
Statut:
epublish
Résumé
Interleukin 7 (IL-7) is a cell growth factor with a central role in normal T cell development, survival and differentiation. The lack of IL-7-IL-7 receptor(R)-mediated signaling compromises lymphoid development, whereas increased signaling activity contributes to the development of chronic inflammation, cancer and autoimmunity. Gain-of-function alterations of the IL-7R and the signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are enriched in T cell acute lymphoblastic leukemia (T-ALL) and autocrine production of IL-7 by T-ALL cells is involved in the phenotypes of leukemic initiation and oncogenic spreading. Several IL-7-associated pathologies are also characterized by increased presence of matrix metalloproteinase-9 (MMP-9), due to neutrophil degranulation and its regulated production by other cell types. Since proteases secreted by neutrophils are known to modulate the activity of many cytokines, we investigated the interactions between IL-7, MMP-9 and several other neutrophil-derived proteases. We demonstrated that MMP-9 efficiently cleaved human IL-7 in the exposed loop between the α-helices C and D and that this process is delayed by IL-7 N-linked glycosylation. Functionally, the proteolytic cleavage of IL-7 did not influence IL-7Rα binding and internalization nor the direct pro-proliferative effects of IL-7 on a T-ALL cell line (HPB-ALL) or in primary CD8
Identifiants
pubmed: 34276694
doi: 10.3389/fimmu.2021.701739
pmc: PMC8278288
doi:
Substances chimiques
Cytokines
0
IL7 protein, human
0
Interleukin-7
0
Serine Proteases
EC 3.4.-
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
701739Informations de copyright
Copyright © 2021 Vandooren, Pereira, Ugarte-Berzal, Rybakin, Noppen, Stas, Bernaerts, Ganseman, Metzemaekers, Schols, Proost and Opdenakker.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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