AQP4-specific T cells determine lesion localization in the CNS in a model of NMOSD
Acta Neuropathologica Communications,
Год журнала:
2025,
Номер
13(1)
Опубликована: Фев. 11, 2025
Abstract
Neuromyelitis
optica
spectrum
disorder
(NMOSD)
is
a
paradigmatic
autoimmune
disease
of
the
central
nervous
system
(CNS),
in
which
water
channel
protein
Aquaporin-4
(AQP4)
targeted
by
self-reactive
immune
response.
While
immunopathology
human
NMOSD
largely
dependent
on
antibodies
to
astrocytic
AQP4,
role
AQP4-specific
T
cells
for
localization
and
quality
lesions
CNS
not
known.
Only
recently,
we
established
that
thymic
B
express
present
AQP4
context
MHC
class
II
molecules
purge
naive
cell
receptor
repertoire
clones.
Here,
exploited
this
finding
investigate
lesion
conditional
AQP4-deficient
(
Aqp4
ΔB
)
mice,
harbor
precursors
their
can
be
sensitized
mount
strong
AQP4(201–220)-specific
CD4
+
Sensitization
mice
with
AQP4(201–220)
was
sufficient
induce
clinical
disease.
The
spatiotemporal
distribution
glial
response
AQP4(201–220)-induced
experimental
encephalomyelitis
(EAE)
compared
classical
MOG(35–55)-induced
EAE
mice.
In
contrast
MOG-EAE,
characterized
midline
brain,
retinal
pathology,
at
grey
matter/white
matter
border
zone
spinal
cord.
Therefore,
conclude
antigen-specific
dictate
NMOSD-lesions
CNS.
Язык: Английский
Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Ноя. 14, 2024
Abstract
The
aquaporin-4
(AQP4)
water
channel
is
essential
in
neurofluid
dynamics.
AQP4
loss
impairs
solute
exchange
between
the
cerebrospinal
fluid
(CSF)
and
interstitial
(ISF).
However,
whether
expression
affects
clearance
from
CSF
space
to
extracranial
remains
unclear.
This
study
aimed
investigate
this
using
dynamic
contrast-enhanced
magnetic
resonance
imaging
(DCE-MRI)
following
intrathecal
administration
of
gadolinium-based
contrast
agents
(GBCAs)
knockout
(KO)
rats.
KO
rats
showed
reduced
efflux
GBCAs
spaces
through
drainage
pathways
increased
retention
compared
with
controls.
These
results
suggest
that
via
pathways.
revealed
a
close
relationship
clearance,
contributing
better
understanding
function
Язык: Английский