STING immune activation of microglia aggravating neurovascular unit damage in diabetic retinopathy
Hongying Li,
No information about this author
Jingfan Wang,
No information about this author
Tianhao Xiao
No information about this author
et al.
Free Radical Biology and Medicine,
Journal Year:
2025,
Volume and Issue:
233, P. 86 - 101
Published: March 30, 2025
Language: Английский
IFNγ preconditioning improves neuroprotection of MSC-derived vesicles on injured retinal ganglion cells by suppressing microglia activation via miRNA-dependent ribosome activity
Tianjing You,
No information about this author
Yi Yang,
No information about this author
A Luodan
No information about this author
et al.
Extracellular Vesicles and Circulating Nucleic Acids,
Journal Year:
2025,
Volume and Issue:
6(1), P. 87 - 111
Published: Feb. 19, 2025
Aim:
Microglial
activation
plays
a
pivotal
role
in
the
pathogenesis
of
retinal
ganglion
cell
(RGC)
degeneration
resulting
from
optic
nerve
crush
(ONC).
Small
extracellular
vesicles
(sEVs)
secreted
by
mesenchymal
stem
cells
(MSCs)
have
potential
to
prevent
modulating
microglial
activation.
In
this
study,
we
elucidated
specific
effects
sEVs
derived
IFN-γ-primed
MSCs
on
phenotypic
transition
microglia
and
associated
pathways
ONC
mice.
Methods:
The
mice
model
was
established
administered
intravitreal
injection
with
native
(native
sEVs)
primed
IFN-γ
(IFNγ-sEVs).
Their
respective
survival
(RGCs)
phenotypes
were
determined
through
visual
function
testing
immunohistochemical
staining.
Combined
mRNA
seq
microRNA
techniques,
mechanism
modulation
transformation
IFNγ.
Results:
It
demonstrated
that
IFNγ-sEVs
exhibited
superior
protective
against
RGC
loss
reduced
inflammatory
responses
retina
compared
sEVs.
Both
types
promoted
disease-associated
(DAM)
phenotype,
while
especially
suppressed
interferon-responsive
(IRM)
during
RGCs
degeneration.
Subsequent
miRNA
sequencing
suggested
miR-423-5p
,
which
most
significant
differential
expression
between
two
elevated
IFNγ-sEVs,
inhibited
IRM
ribosomal
genes.
Conclusion:
These
findings
suggest
IFN-γ-preconditioned
may
enhance
neuroprotection
suppressing
secretion
containing
microRNAs
Language: Английский
Advances in understanding the role and mechanism of the cGAS-STING signaling pathway in ocular diseases
Mengdi Zhang,
No information about this author
Jiayu Xu,
No information about this author
Wenjia Qu
No information about this author
et al.
Immunological Medicine,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 15
Published: March 8, 2025
The
cGAS-STING
signaling
pathway
plays
a
critical
role
in
the
immune
defense
against
DNA
viruses
and
autoimmunity,
coordinating
cascade
of
events
that
enhance
cytokine
production,
particularly
type
I
interferons.
This
review
summarizes
recent
advancements
understanding
pathway's
impact
on
various
ocular
diseases,
including
age-related
macular
degeneration
(AMD),
diabetic
retinopathy,
uveitis.
Activation
this
by
cytoplasmic
from
either
damaged
retinal
cells
or
external
pathogens
induces
inflammatory
responses
may
accelerate
disease
progression.
Moreover,
paper
explores
new
therapeutic
approaches
target
pathway,
offering
insights
into
how
modulation
could
reduce
inflammation
improve
clinical
outcomes.
emerging
research
area
suggests
potential
for
innovative
treatments
degenerative
conditions.
Language: Английский
TRIM21 promotes type I interferon by inhibiting the autophagic degradation of STING via p62/SQSTM1 ubiquitination in systemic lupus erythematosus
Chen Li,
No information about this author
Ang Ma,
No information about this author
Yu Bai
No information about this author
et al.
Acta Biochimica et Biophysica Sinica,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
The
cGAS-STING
signaling
pathway
serves
as
a
pivotal
surveillance
mechanism
for
cytosolic
double-stranded
DNA
(dsDNA)
detection
in
mammalian
systems.
While
STING-mediated
type
I
interferon
production
is
crucial
host
defense,
sustained
activation
of
this
contributes
to
autoimmune
pathologies,
including
systemic
lupus
erythematosus
(SLE).
Maintaining
immune
homeostasis
requires
precise
regulation
STING
activity
prevent
hyperactivation.
Our
study
identifies
TRIM21
novel
positive
regulator
SLE
pathogenesis.
results
demonstrate
that
overexpression
stabilizes
by
suppressing
autophagic
degradation,
whereas
depletion
accelerates
clearance
process.
Mechanistically,
catalyzes
the
K63-linked
polyubiquitylation
selective
autophagy
receptor
p62/SQSTM1,
disrupting
its
interaction
with
STING.
This
post-translational
modification
prevents
sequestration
into
autophagosomes,
thereby
stabilizing
adaptor
protein
and
amplifying
downstream
responses.
findings
reveal
previously
unrecognized
regulatory
circuit
which
orchestrates
cross-talk
between
ubiquitin
control
turnover.
TRIM21-p62
axis
represents
potential
therapeutic
target
attenuating
pathological
STING-dependent
disorders.
work
advances
our
understanding
demonstrating
how
E3
ligase-mediated
modifications
modulate
cargo
recognition
pathways.
identified
provides
new
insights
molecular
interplay
ubiquitylation
degradation
maintaining
innate
balance,
offering
perspectives
developing
targeted
therapies
against
interferonopathies
associated
hyperactivity.
Language: Английский
Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy
Lai-Yang Zhou,
No information about this author
Zhen-Gang Liu,
No information about this author
Sun Yong-quan
No information about this author
et al.
Cell Regeneration,
Journal Year:
2025,
Volume and Issue:
14(1)
Published: April 2, 2025
Retinal
ganglion
cells
(RGCs)
are
the
visual
gateway
of
brain,
with
their
axons
converging
to
form
optic
nerve,
making
them
most
vulnerable
target
in
diseases
such
as
glaucoma
and
traumatic
neuropathy
(TON).
In
both
diseases,
disruption
blood-retinal
barrier(BRB)
is
considered
an
important
mechanism
that
accelerates
RGC
degeneration
hinders
axon
regeneration.
The
BRB
consists
inner
barrier
(iBRB)
outer
(oBRB),
which
maintained
by
endothelial
cells(ECs),
pericytes(PCs),
retinal
pigment
epithelial
(RPE),
respectively.
Their
functions
include
regulating
nutrient
exchange,
oxidative
stress,
immune
microenvironment.
However,
TON,
structural
functional
integrity
severely
damaged
due
mechanical
inflammatory
reactions,
metabolic
disorders.
Emerging
evidence
highlights
leads
heightened
vascular
permeability,
cell
infiltration,
sustained
chronic
inflammation,
creating
a
hostile
microenvironment
for
survival.
Furthermore,
dynamic
interplay
imbalance
among
ECs,
PCs,
glial
within
neurovascular
unit
(NVU)
pivotal
drivers
destruction,
exacerbating
apoptosis
limiting
nerve
intricate
molecular
cellular
mechanisms
underlying
these
processes
underscore
BRB's
critical
role
TON
pathophysiology
while
offering
compelling
foundation
therapeutic
strategies
targeting
repair
stabilization.
This
review
provides
crucial
insights
lays
robust
groundwork
advancing
research
on
neural
regeneration
innovative
protective
strategies.
Language: Английский
cGAS, an innate dsDNA sensor with multifaceted functions
Cell Insight,
Journal Year:
2025,
Volume and Issue:
4(3), P. 100249 - 100249
Published: April 17, 2025
Cyclic
GMP-AMP
synthase
(cGAS)
functions
as
a
pivotal
intracellular
sensor
for
the
innate
immune
sensing
of
double-stranded
DNA
(dsDNA),
monitoring
those
nucleic
acids
from
foreign
and
endogenous
sources.
Upon
assembling
into
cellular
condensates
with
dsDNA
regulators,
cGAS
synthesizes
2'3'-cGAMP
that
activates
downstream
STING
signaling.
This
activation
triggers
variety
responses,
including
autophagy,
mRNA
translation,
interferon
signaling,
inflammatory
responses.
Context-dependently,
resides
in
diverse
compartments,
nucleus,
micronuclei,
plasma
membrane,
organelle
surfaces.
Beyond
its
DNA-sensing
role,
can
play
complex
roles
these
locations,
such
damage
repairing,
membrane
restoration,
chromatin
condensation,
angiogenesis,
aging
regulation.
comprehensive
review
summarizes
recent
advances
activation,
regulation,
pharmacological
management
cGAS,
focusing
on
molecular
mechanisms,
post-translational
modifications
(PTMs),
therapeutic
interventions.
The
functional
implications
various
disease
contexts,
infectious
diseases,
autoinflammatory
autoimmune
aging,
cancers,
are
also
covered.
Language: Английский
cGAS/STING signalling in macrophages aggravates obliterative bronchiolitis via an IFN‐α‐dependent mechanism after orthotopic tracheal transplantation in mice
Junhao Wan,
No information about this author
Hao Liu,
No information about this author
Chuangyan Wu
No information about this author
et al.
Clinical and Translational Medicine,
Journal Year:
2025,
Volume and Issue:
15(5)
Published: April 28, 2025
Abstract
Background
Our
previous
findings
have
underscored
the
role
of
innate
immunity
in
obliterative
bronchiolitis
(OB).
However,
despite
central
importance
cyclic
GMP‒AMP
synthase
(cGAS)/stimulator
interferon
genes
(STING)
signalling
pathway
immune
responses,
its
specific
contribution
to
OB
progression
remains
largely
unexplored.
Methods
A
murine
orthotopic
tracheal
transplantation
model
was
established
replicate
pathogenesis.
RNA
sequencing
and
single‐cell
data
were
analysed
investigate
mechanisms
underlying
OB.
Key
molecules
cGAS/STING
assessed
using
immunofluorescence
staining.
Macrophage‐specific
Sting1
knockout
mice
generated
Haematoxylin
eosin
staining
Masson's
trichrome
utilised
evaluate
allograft
stenosis
fibrosis.
Immune
cell
infiltration
cytokine
expression
qRT‐PCR.
Flow
cytometry
used
characterise
splenic
T‐cell
subsets
assess
co‐stimulatory
molecule
macrophages.
Results
The
upregulated
macrophages
infiltrating
allografts.
significantly
attenuated
alloreactive
responses
alleviated
Furthermore,
deletion
reduced
inflammatory
marker
NOS2,
antigen‐presenting
MHC
class
II
(CD80
CD86)
Mechanistically,
inhibited
production
interferon‐α2
(IFN‐α2),
while
protective
effect
macrophage‐specific
Sting
reversed
by
IFN‐α2
administration.
Importantly,
STING
inhibition
enhanced
tolerance‐promoting
effects
cytotoxic
T‐lymphocyte‐associated
antigen
4‐Ig
(CTLA4‐Ig),
leading
preservation
airway
epithelium.
Conclusions
study
demonstrated
that
exacerbated
rejection
an
IFN‐α2‐dependent
manner.
These
provide
insights
into
potential
novel
strategies
for
prolonging
survival.
points
activated
rejection,
promoted
ability
potentiated
therapeutic
efficacy
CTLA4‐Ig
Language: Английский
Microglia remodeling in the visual thalamus of the DBA/2J mouse model of glaucoma
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(5), P. e0323513 - e0323513
Published: May 15, 2025
Microglia
are
the
resident
immune
cells
of
central
nervous
system
and
mediate
a
broad
array
adaptations
during
disease,
injury,
development.
Typically,
microglia
morphology
is
understood
to
provide
window
into
their
function
have
capacity
adopt
spectrum
functional
phenotypes
characterized
by
numerous
morphologies
gene
expression
profiles.
Glaucoma,
which
leads
blindness
from
retinal
ganglion
cell
(RGC)
degeneration,
commonly
associated
with
elevated
intraocular
pressure
(IOP)
triggers
responses
within
layers,
at
optic
nerve
head,
in
projection
targets
brain.
The
goal
this
study
was
determine
relationship
loss
RGC
output
synapses
dorsolateral
geniculate
nucleus
(dLGN),
target
thalamus
that
conveys
information
primary
visual
cortex.
We
accomplished
analyzing
dLGN
sections
DBA/2J
mice,
develop
form
inherited
glaucoma,
4,
9,
12
months
age,
representing
distinct
time
points
disease
progression.
analyzed
using
skeletonized
Iba1
fluorescence
images
fractal
analyses
individually
reconstructed
cells.
found
older
mice
adopted
simplified
morphologies,
fewer
endpoints
less
total
process
length
per
cell.
There
an
age-dependent
shift
tissue
control
(DBA/2J
Gpnmb+
)
accelerated
mice.
Measurements
correlated
cumulative
IOP,
immunofluorescence
labeling
for
complement
component
C1q,
vGluT2-labeled
axon
terminal
density.
Additionally,
analysis
revealed
clear
distinction
between
glaucomatous
dLGN,
ocular
hypertensive
showing
elongated
rod-like
morphology.
RNA-sequencing
showed
upregulation
system-related
genes.
These
results
suggest
alter
physiology
respond
degeneration
potentially
contributing
CNS
neurodegenerative
vision
loss.
Language: Английский
Targeting Mitochondrial Dysfunction: Innovative Strategies to Combat Glaucoma Neuroinflammation
Experimental Eye Research,
Journal Year:
2025,
Volume and Issue:
unknown, P. 110441 - 110441
Published: May 1, 2025
Language: Английский
STING deletion protects against amyloid β–induced Alzheimer's disease pathogenesis
Alzheimer s & Dementia,
Journal Year:
2025,
Volume and Issue:
21(5)
Published: May 1, 2025
Abstract
INTRODUCTION
While
immune
dysfunction
has
been
increasingly
linked
to
Alzheimer's
disease
(AD)
progression,
many
major
innate
signaling
molecules
have
yet
be
explored
in
AD
pathogenesis
using
genetic
targeting
approaches.
METHODS
To
investigate
a
role
for
the
key
adaptor
molecule,
stimulator
of
interferon
genes
(STING),
AD,
we
deleted
Sting1
5xFAD
mouse
model
AD‐related
amyloidosis
and
evaluated
effects
on
pathology,
neuroinflammation,
gene
expression,
cognition.
RESULTS
Genetic
ablation
STING
mice
led
improved
control
amyloid
beta
(Aβ)
plaques,
alterations
microglial
activation
status,
decreased
levels
neuritic
dystrophy,
protection
against
cognitive
decline.
Moreover,
rescue
neurological
STING‐deficient
was
characterized
by
reduced
expression
type
I
both
microglia
excitatory
neurons.
DISCUSSION
These
findings
reveal
critical
roles
Aβ‐driven
suggest
that
STING‐targeting
therapeutics
may
offer
promising
strategies
treat
AD.
Highlights
Stimulator
(STING)
deficiency
disease‐related
results
deposition
altered
status.
Protection
is
associated
with
involved
IFN
signaling,
neuronal
health,
oxidative
stress.
Loss
leads
spatial
learning
memory.
Language: Английский