Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 8, 2025
The
critical
role
of
the
immune
system
in
brain
function
and
dysfunction
is
well
recognized,
yet
development
therapies
for
psychiatric
diseases
has
been
slow
due
to
concerns
about
iatrogenic
deficiencies.
These
are
emphasized
by
lack
objective
diagnostic
tools
psychiatry.
A
promise
resolve
this
conundrum
lies
exploitation
extracellular
vesicles
(EVs)
that
physiologically
produced
or
can
be
synthetized.
EVs
regulate
recipient
cell
functions
offer
potential
EVs-based
therapies.
Intranasal
administration
enables
targeting
specific
regions
functions,
thereby
facilitating
design
precise
treatments
diseases.
such
requires
navigating
four
dynamically
interacting
networks:
neuronal,
glial,
immune,
EVs.
networks
profoundly
influenced
fluid
distribution.
They
crucial
homeostasis,
cellular
intercellular
communication.
Fluid
abnormalities,
like
edema
altered
cerebrospinal
(CSF)
dynamics,
disrupt
these
networks,
negatively
impacting
health.
deeper
understanding
above-mentioned
vital
creating
biomarker
panels
identify
distinct
patient
subsets
with
similar
neuro-behavioral
symptoms.
Testing
functional
pathways
biomarkers
could
lead
new
therapeutic
tools.
Regulatory
approval
will
depend
on
robust
preclinical
data
reflecting
progress
interdisciplinary
areas,
which
pave
way
innovative
treatments.
Highly
collaborative
teams
needed
achieve
ambitious
goals.
Язык: Английский
Lung disease in relation to unique monocyte-macrophage subpopulations induced by combined inhalant endotoxin and collagen-induced arthritis
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 9, 2025
Lung
disease
is
the
most
overrepresented
cause
of
death
in
rheumatoid
arthritis
(RA).
Animal
studies
have
demonstrated
potentiated
autoimmunity,
arthritis,
and
profibrotic/inflammatory
lung
with
a
combination
airborne
exposures
collagen-induced
(CIA),
model
that
recapitulates
features
RA-associated
interstitial
(RA-ILD).
As
patients
RA-ILD
demonstrate
unique
circulating
monocyte
subpopulations,
this
study
aims
to
characterize
infiltrating
monocytes/macrophages
mouse
determine
whether
reducing
these
cells
mitigates
development
disease.
Autoimmune-prone
DBA/1J
mice
received
intranasal
inhalation
lipopolysaccharide
(LPS)
daily
for
up
5
weeks
CIA
induction.
Experimental
groups
included
Sham
(saline
injection/saline
inhalation),
(CIA/saline),
LPS
(saline/LPS),
CIA+LPS
(CIA/LPS).
was
assessed
by
longitudinal
imaging,
function
measurements,
bronchoalveolar
lavage
fluid,
tissues,
histopathology.
Cell
subpopulations
were
analyzed
single
cell
RNA-sequencing
flow
cytometry.
Intravenous
clodronate
liposome
administration
employed
reduce
monocytes.
Longitudinal
imaging
increased
volume
tissue
density
mice.
assessment
showed
reduced
compliance
airway
resistance
dual
exposure.
Unsupervised
clustering
revealed
16
discrete
clusters
among
experimental
robust
overlapping
characteristics
both
CIA.
By
cytometry,
exposure
induced
activated
CD11c+CD206+CD11b+MHC
Class
IIhiCD80+
alveolar
macrophages,
CD11cmidCD206-CD11b+Ly6Chi(and
Ly6Clo)MHC
IIhiCD80+CD86+
CD11c-CD11b+Ly6ChiMHC
monocytic-like
cells.
MHC
IIhi-expressing
across
monocyte/macrophage
treated
more
aligned
than
alone.
CIA+LPS-induced
CD11c+CD11b+
CD11cmidCD11b+
neutrophils,
lymphocytes,
inflammatory/pro-fibrotic
mediators,
expression
vimentin
citrullinated
malondialdehyde
acetaldehyde
(MAA)-modified
proteins/lung
autoantigens.
The
interaction
inhalation-induced
inflammation
autoimmune
results
associated
uniquely
inflammatory
macrophages.
Moreover,
depletion
monocytes
attenuated
Whereas
macrophage
immunophenotype
endotoxin
exposure,
co-exposure
modeling
renders
potentially
inform
pathogenesis
treatment
RA-ILD.
Язык: Английский
Unveiling the Emerging Role of Extracellular Vesicle–Inflammasomes in Hyperoxia-Induced Neonatal Lung and Brain Injury
Cells,
Год журнала:
2024,
Номер
13(24), С. 2094 - 2094
Опубликована: Дек. 18, 2024
Extremely
premature
infants
are
at
significant
risk
for
developing
bronchopulmonary
dysplasia
(BPD)
and
neurodevelopmental
impairment
(NDI).
Although
BPD
is
a
predictor
of
poor
outcomes,
it
currently
unknown
how
contributes
to
brain
injury
long-term
NDI
in
pre-term
infants.
Extracellular
vesicles
(EVs)
small,
membrane-bound
structures
released
from
cells
into
the
surrounding
environment.
EVs
involved
inter-organ
communication
diverse
pathological
processes.
Inflammasomes
large,
multiprotein
complexes
that
part
innate
immune
system
responsible
triggering
inflammatory
responses
cell
death.
Apoptosis-associated
speck-like
protein
containing
caspase
recruitment
domain
(ASC)
pivotal
inflammasome
assembly
activating
caspase-1.
Activated
caspase-1
cleaves
gasdermin
D
(GSDMD)
release
30
kD
N-terminal
can
form
membrane
pores,
leading
lytic
death,
also
known
as
pyroptosis.
cleave
pro-IL-1β
pro-IL-18
their
active
forms,
which
be
rapidly
through
GSDMD
pores
induce
inflammation.
Recent
evidence
has
emerged
activation
inflammasomes
associated
with
neonatal
lung
injury,
inhibition
reduces
hyperoxia-induced
injury.
Additionally,
multiple
studies
have
demonstrated
hyperoxia
stimulates
lung-derived
contain
cargos.
Adoptive
transfer
these
circulation
normal
mice
rats
induces
This
review
focuses
on
EV–inflammasomes’
roles
mediating
lung-to-brain
crosstalk
via
EV-dependent
EV-independent
mechanisms
critical
BPD,
pathogenesis.
EV–inflammasomes
will
discussed
potential
therapeutic
targets
Язык: Английский
Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs
Biology,
Год журнала:
2024,
Номер
13(12), С. 1056 - 1056
Опубликована: Дек. 16, 2024
Bidirectional
communication
between
the
central
nervous
system
(CNS)
and
peripheral
organs
tissue
has
been
widely
documented
in
physiological
pathological
conditions.
This
relies
on
bilateral
transmission
of
signaling
molecules
substances
that
circulate
throughout
body
reach
their
target
site(s)
via
blood
other
biological
fluids
(e.g.,
cerebrospinal
fluid,
lymph).
One
mechanisms
by
which
these
molecular
messengers
are
exchanged
is
through
secretion
extracellular
vesicles
(EVs).
EVs
known
to
mediate
cell-to-cell
delivering
molecules,
including
nucleic
acids,
proteins,
lipids,
various
bioactive
regulators.
Moreover,
can
cross
blood–brain
barrier
(BBB),
enabling
direct
periphery
brain.
In
particular,
delivery
microRNAs
(miRNAs)
modulate
expression
profiles
recipient
cells,
thereby
influencing
functions.
review
synthesizes
current
findings
about
brain–periphery
cross-talk
mediated
EVs-delivered
miRNAs.
Although
this
mechanism
definitively
shown
a
few
cases,
much
evidence
indirectly
indicates
it
could
brain–peripherical
organs/tissue
communication,
especially
Therefore,
understanding
process
provide
valuable
insights
for
treatment
management
neurological
systemic
diseases.
Язык: Английский