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Single-Cell RNA sequencing identifies NAMPT as a potential therapeutic target in autoimmune uveitis
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DOI：10.1016/j.jare.2025.12.030.png)
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Abstract
En 中文
• Inhibition of NAMPT significantly ameliorates both the clinical symptoms and histopathological features of EAU. • NAMPT inhibition reverses abnormal, disease-associated transcriptional programs within immune cell populations in EAU, particularly in CD4+ T cells. • Suppressing NAMPT reduces Th17 and Th1 responses while enhancing Treg populations. • NAMPT inhibition restores the Teff/Treg balance by downregulating Hif1α. • NAMPT expression is elevated in CD4+ T cells from patients with uveitis. • A conserved NAMPT-Hif1α signaling axis exists in human uveitis.
Keywords:
Autoimmune uveitis
NAMPT
Hif1α
Single-cell RNA sequencing
NAMPT
Nicotinamide phosphoribosyltransferase
PBMCs
Peripheral blood mononuclear cells
VKH
Vogt-Koyanagi-Harada
Th17
T helper 17
Th1
T helper 1
HC
Healthy controls
Treg/TREG
Regulatory T cell
CFA
Complete Freund’s adjuvant
IRBP1-20
Human interphotoreceptor retinoid-binding protein 1–20
PBS
Phosphate-buffered saline
EAU
Experimental autoimmune uveitis
CDLN
Cervical draining lymph node
scRNA-seq
Single-cell RNA sequencing
PTX
Pertussis toxin
H&E
Hematoxylin and Eosin
NAMPTi
NAMPTi-treated EAU mice
UMAP
Uniform Manifold Approximation and Projection
TC
T cells
BC
B cells
NK
Natural killer cells
pDC/PDC
Plasmacytoid dendritic cells
cDC/CDC
Conventional dendritic cells
Macro
Macrophages
Mono/MONO
Monocytes
Neu
Neutrophils
NCD4
Naïve CD4+ T cells
NCD8
Naïve CD8+ T cells
Tfh
T follicular helper cells
Pro-T
Proliferative T cells
Ctl
Cytotoxic T lymphocytes
NBC
Naïve B cells
PC
Plasma cells
GC
Germinal center B cells
L-R
Ligand-Receptor
CD4TC
CD4+ T cells
CD8TC
CD8+ T cells
TEM
Effector memory T cells
DEG
Differentially expressed gene
Hif1α
Hypoxia-inducible factor 1 alpha
GO
Gene Ontology
Teff
Effector T cells
Journal
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