Science Signaling,
Год журнала:
2024,
Номер
17(833)
Опубликована: Апрель 23, 2024
Upon
activation,
T
cells
undergo
metabolic
reprogramming
to
meet
the
bioenergetic
demands
of
clonal
expansion
and
effector
function.
Because
dysregulated
cell
cytokine
production
phenotypes
coexist
in
chronic
inflammatory
disease,
including
rheumatoid
arthritis
(RA),
we
investigated
whether
cytokines
released
by
differentiating
amplified
their
changes.
We
found
that
tumor
necrosis
factor–α
(TNF-α)
human
naïve
CD4
+
upon
activation
stimulated
expression
a
transcriptome
increased
glycolysis,
amino
acid
uptake,
mitochondrial
oxidation
glutamine,
biogenesis.
The
effects
TNF-α
were
mediated
Akt-mTOR
signaling
kinase
ITK
did
not
require
NF-κB
pathway.
differentiation
into
proinflammatory
helper
1
(T
H
1)
17
cells,
but
regulatory
cells.
from
patients
with
RA
showed
consequent
Akt
phosphorylation
activation.
These
also
exhibited
mass,
particularly
within
subsets
implicated
disease.
Together,
these
findings
suggest
cell–derived
drives
promoting
through
ITK,
Akt,
mTOR,
which
is
autoinflammatory
Circulation Research,
Год журнала:
2022,
Номер
130(8), С. 1167 - 1186
Опубликована: Апрель 14, 2022
Inflammation
and
immune
mechanisms
are
crucially
involved
in
the
pathophysiology
of
development,
acute
damage
cascades,
chronic
course
after
ischemic
stroke.
Atherosclerosis
is
an
inflammatory
disease,
and,
addition
to
classical
risk
factors,
maladaptive
lead
increased
Accordingly,
individuals
with
signs
inflammation
or
corresponding
biomarkers
have
Anti-inflammatory
drugs,
such
as
IL
(interleukin)-1β
blockers,
methotrexate,
colchicine,
represent
attractive
treatment
strategies
prevent
vascular
events
Lately,
COVID-19
pandemic
shows
a
clear
association
between
SARS-CoV2
infections
cerebrovascular
events.
Furthermore,
both
innate
adaptive
systems
influence
cerebral
cascades
Neutrophils,
monocytes,
microglia,
well
T
B
lymphocytes
each
play
complex
interdependent
roles
that
synergize
remove
dead
tissue
but
also
can
cause
bystander
injury
intact
brain
cells
generate
inflammation.
Chronic
systemic
comorbid
may
unfavorably
outcome
stroke
recurrence
for
further
In
addition,
triggers
specific
depression,
which
turn
promote
infections.
Recent
research
now
increasingly
addressing
question
extent
long-term
particular,
complications
poststroke
dementia
even
depression.
Cell Metabolism,
Год журнала:
2023,
Номер
35(4), С. 633 - 650.e9
Опубликована: Март 9, 2023
The
metabolic
state
represents
a
major
hurdle
for
an
effective
adoptive
T
cell
therapy
(ACT).
Indeed,
specific
lipids
can
harm
CD8+
(CTL)
mitochondrial
integrity,
leading
to
defective
antitumor
responses.
However,
the
extent
which
affect
CTL
functions
and
fate
remains
unexplored.
Here,
we
show
that
linoleic
acid
(LA)
is
positive
regulator
of
activity
by
improving
fitness,
preventing
exhaustion,
stimulating
memory-like
phenotype
with
superior
effector
functions.
We
report
LA
treatment
enhances
formation
ER-mitochondria
contacts
(MERC),
in
turn
promotes
calcium
(Ca2+)
signaling,
energetics,
As
direct
consequence,
potency
LA-instructed
CD8
cells
vitro
vivo.
thus
propose
as
ACT
potentiator
tumor
therapy.
Nature,
Год журнала:
2023,
Номер
620(7972), С. 200 - 208
Опубликована: Июль 5, 2023
Abstract
Cancer
cells
evade
T
cell-mediated
killing
through
tumour–immune
interactions
whose
mechanisms
are
not
well
understood
1,2
.
Dendritic
(DCs),
especially
type-1
conventional
DCs
(cDC1s),
mediate
cell
priming
and
therapeutic
efficacy
against
tumours
3
DC
functions
orchestrated
by
pattern
recognition
receptors
3–5
,
although
other
signals
involved
remain
incompletely
defined.
Nutrients
emerging
mediators
of
adaptive
immunity
6–8
but
whether
nutrients
affect
function
or
communication
between
innate
immune
is
largely
unresolved.
Here
we
establish
glutamine
as
an
intercellular
metabolic
checkpoint
that
dictates
tumour–cDC1
crosstalk
licenses
cDC1
in
activating
cytotoxic
cells.
Intratumoral
supplementation
inhibits
tumour
growth
augmenting
cDC1-mediated
CD8
+
immunity,
overcomes
resistance
to
blockade
immunotherapies.
Mechanistically,
cDC1s
compete
for
uptake
via
the
transporter
SLC38A2
tune
anti-tumour
immunity.
Nutrient
screening
integrative
analyses
show
dominant
amino
acid
promoting
function.
Further,
signalling
FLCN
impinges
on
TFEB
Loss
selectively
impairs
vivo
a
TFEB-dependent
manner
phenocopies
deficiency
eliminating
effect
supplementation.
Our
findings
glutamine-mediated
underpins
evasion,
reveal
acquisition
limiting
events
activation
putative
targets
cancer
treatment.
Cell Metabolism,
Год журнала:
2022,
Номер
34(9), С. 1298 - 1311.e6
Опубликована: Авг. 17, 2022
How
environmental
nutrient
availability
impacts
T
cell
metabolism
and
function
remains
poorly
understood.
Here,
we
report
that
the
presence
of
physiologic
carbon
sources
(PCSs)
in
culture
medium
broadly
glucose
utilization
by
CD8+
cells,
independent
transcriptional
changes
metabolic
reprogramming.
The
PCSs
reduced
contribution
to
TCA
cycle
increased
effector
with
lactate
directly
fueling
cycle.
In
fact,
cells
responding
Listeria
infection
preferentially
consumed
over
as
a
substrate
vitro,
enhancing
bioenergetic
biosynthetic
capacity.
Inhibiting
lactate-dependent
silencing
dehydrogenase
A
(Ldha)
impaired
both
homeostasis
proliferative
expansion
vivo.
Together,
our
data
indicate
source
shapes
identifies
fuel
for
cells.
