CD98 defines a metabolically flexible, proinflammatory subset of low-density neutrophils in systemic lupus erythematosus.
CD98
granulocyte colony-stimulating factor
low-density neutrophils
systemic lupus erythematosus
Journal
Clinical and translational medicine
ISSN: 2001-1326
Titre abrégé: Clin Transl Med
Pays: United States
ID NLM: 101597971
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
30
11
2022
received:
24
05
2022
accepted:
06
12
2022
entrez:
18
1
2023
pubmed:
19
1
2023
medline:
21
1
2023
Statut:
ppublish
Résumé
Low-density neutrophils (LDN) are a distinct subset of neutrophils rarely detected in healthy people but appear in the blood of patients with autoimmune diseases, including systemic lupus erythematosus (SLE), and are mobilised in response to granulocyte colony-stimulating factor (G-CSF). The aim of this study was to identify novel mechanisms responsible for the pathogenic capacity of LDN in SLE. Neutrophils were isolated from donors treated with G-CSF, and whole-cell proteomic analysis was performed on LDN and normal-density neutrophils. CD98 is significantly upregulated in LDN from G-CSF donors and defines a subset of LDN within the blood of SLE patients. CD98 is a transmembrane protein that dimerises with L-type amino acid transporters. We show that CD98 is responsible for the increased bioenergetic capacity of LDN. CD98 on LDN mediates the uptake of essential amino acids that are used by mitochondria to produce adenosine triphosphate, especially in the absence of glucose. Inhibition of CD98 reduces the metabolic flexibility of this population, which may limit their pathogenic capacity. CD98 CD98 provides a phenotypic marker for LDN that facilitates identification of this population without density-gradient separation and represents a novel therapeutic target to limit its pathogenic capacity.
Sections du résumé
BACKGROUND
Low-density neutrophils (LDN) are a distinct subset of neutrophils rarely detected in healthy people but appear in the blood of patients with autoimmune diseases, including systemic lupus erythematosus (SLE), and are mobilised in response to granulocyte colony-stimulating factor (G-CSF). The aim of this study was to identify novel mechanisms responsible for the pathogenic capacity of LDN in SLE.
METHODS
Neutrophils were isolated from donors treated with G-CSF, and whole-cell proteomic analysis was performed on LDN and normal-density neutrophils.
RESULTS
CD98 is significantly upregulated in LDN from G-CSF donors and defines a subset of LDN within the blood of SLE patients. CD98 is a transmembrane protein that dimerises with L-type amino acid transporters. We show that CD98 is responsible for the increased bioenergetic capacity of LDN. CD98 on LDN mediates the uptake of essential amino acids that are used by mitochondria to produce adenosine triphosphate, especially in the absence of glucose. Inhibition of CD98 reduces the metabolic flexibility of this population, which may limit their pathogenic capacity. CD98
CONCLUSIONS
CD98 provides a phenotypic marker for LDN that facilitates identification of this population without density-gradient separation and represents a novel therapeutic target to limit its pathogenic capacity.
Identifiants
pubmed: 36653319
doi: 10.1002/ctm2.1150
pmc: PMC9849148
doi:
Substances chimiques
Cytokines
0
Granulocyte Colony-Stimulating Factor
143011-72-7
Fusion Regulatory Protein-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1150Informations de copyright
© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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