The prognostic impact of SIGLEC5-induced impairment of CD8
Biomarker
HIF1α
Immune checkpoint
SIGLEC5
Sepsis
T-cell exhaustion
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
21
06
2023
revised:
22
09
2023
accepted:
06
10
2023
medline:
13
11
2023
pubmed:
28
10
2023
entrez:
27
10
2023
Statut:
ppublish
Résumé
Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8 SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).
Sections du résumé
BACKGROUND
BACKGROUND
Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis.
METHODS
METHODS
In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100).
FINDINGS
RESULTS
SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8
INTERPRETATION
CONCLUSIONS
SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients.
FUNDING
BACKGROUND
Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).
Identifiants
pubmed: 37890368
pii: S2352-3964(23)00407-3
doi: 10.1016/j.ebiom.2023.104841
pmc: PMC10630607
pii:
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, Myelomonocytic
0
Lectins
0
Ligands
0
SIGLEC5 protein, human
0
Siglecf protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104841Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests We declare that none of the authors have any conflicts of interest with the content of this manuscript.