AX-024 Inhibits Antigen-Specific T-Cell Response and Improves Intracerebral Hemorrhage Outcomes in Mice
Stroke,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 27, 2025
BACKGROUND:
Stroke-induced
opposite
T-cell
responses
in
the
peri-lesion
area
and
periphery
worsen
stroke
outcomes
by
aggravating
brain
injury
or
increasing
infectious
complications,
respectively.
Despite
their
well-known
role
T
lymphocyte
activation,
impact
of
TCRs
(T-cell
receptors)
on
remains
poorly
understood.
In
this
study,
we
investigated
causal
link
between
observed
intracerebral
hemorrhage
(ICH).
METHODS:
We
established
ICH
model
injecting
collagenase
VII-S
into
left
striatum
young
adult
(10–12
weeks)
male
female
aged
(18–20
months)
C57BL/6
mice.
intraperitoneally
administered
AX-024,
a
small
molecule
inhibitor
TCR
signaling,
evaluated
results
using
flow
cytometry,
Western
blotting,
immunofluorescence
staining,
histological
bacterial
culture,
behavioral
tests.
RESULTS:
Our
findings
mice
indicate
that
administering
AX-024
within
48
hours
suppressed
activation
nonspecific
antigen-specific
CD3
(cluster
differentiation
3)
+
CD4
CD8
cells
36
3
days
after
but
not
7
after.
Additionally,
it
temporarily
inhibited
at
above
2
time
points.
It
also
reduced
molecular
cellular
neuroinflammation
hemorrhagic
early
ICH.
These
effects
ultimately
improved
while
having
no
lung
loads.
This
can
be
further
supported
similar
with
CONCLUSIONS:
may
represent
promising
option
for
mitigating
detrimental
entering
damaged
without
loads
The
potential
as
potent
immunosuppressive
treatment
is
an
exciting
prospect
warrants
investigation.
Language: Английский
The characteristics of T‐cell receptor repertoire in relation to systemic immune response of patients with ischemic stroke
Journal of Neurochemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 22, 2024
T
lymphocytes
play
a
vital
role
in
the
immune-inflammatory
response
following
stroke.
However,
specific
mechanisms
behind
contrasting
functions
of
cells
brain
and
peripheral
tissues
after
stroke
remain
unclear
require
further
investigation.
T-cell
receptors
(TCRs)
are
essential
controlling
how
develop
become
active.
This
study
aims
to
gain
deeper
understanding
biological
function
by
analyzing
TCR
repertoire
patients
who
have
experienced
an
acute
ischemic
(AIS).
High-throughput
sequencing
was
conducted
on
blood
samples
from
25
AIS
10
healthy
controls.
We
compared
percentage
characteristics
repertoire,
specifically
focusing
recombination
V(D)J
gene
fragments
diversity
complementarity
determining
region
3
(CDR3)
Vβ
gene.
Additionally,
this
analyzed
potential
significance
skewed
patients.
In
with
AIS,
proportion
circulating
(LY%)
decreased
while
systemic
index
(SII)
increased
The
average
number
read
pairs
decreased,
corresponding
presence
lymphopenia.
fragments,
CDR3
clonotypes,
elevated
Furthermore,
amino
acid
or
nucleotide
clonotypes
negatively
correlated
neurologic
deficits
but
positively
patients'
immune
condition
functional
outcomes.
Our
findings
suggest
that
both
immunosuppression
enhanced
antigen-specific
may
exist
periphery
Further
investigation
into
underlying
these
opposing
changes
lead
discovery
novel
targets
reverse
mitigate
detrimental
effects
lesioned
Language: Английский