Engineered IL-10 variants elicit potent immunomodulatory effects at low ligand doses.
Animals
CD8-Positive T-Lymphocytes
/ cytology
Cell Movement
/ genetics
Cells, Cultured
Energy Metabolism
/ genetics
Gene Expression Profiling
/ methods
Humans
Interleukin-10
/ genetics
Ligands
Monocytes
/ cytology
Mutation
/ immunology
Protein Binding
Receptors, Interleukin-10
/ genetics
STAT1 Transcription Factor
/ genetics
STAT3 Transcription Factor
/ genetics
Sf9 Cells
Signal Transduction
/ genetics
Spodoptera
Journal
Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
entrez:
16
9
2020
pubmed:
17
9
2020
medline:
30
10
2021
Statut:
epublish
Résumé
Interleukin-10 (IL-10) is a dimeric cytokine with both immunosuppressive and immunostimulatory activities; however, IL-10-based therapies have shown only marginal clinical benefits. Here, we explored whether the stability of the IL-10 receptor complex contributes to the immunomodulatory potency of IL-10. We generated an IL-10 mutant with enhanced affinity for its IL-10Rβ receptor using yeast surface display. Compared to the wild-type cytokine, the affinity-enhanced IL-10 variants recruited IL-10Rβ more efficiently into active cell surface signaling complexes and triggered greater STAT1 and STAT3 activation in human monocytes and CD8
Identifiants
pubmed: 32934073
pii: 13/649/eabc0653
doi: 10.1126/scisignal.abc0653
pmc: PMC7685028
mid: NIHMS1636869
pii:
doi:
Substances chimiques
Ligands
0
Receptors, Interleukin-10
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI097629
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143554
Pays : United States
Organisme : Wellcome Trust
ID : 202323/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203752/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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