Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 30, 2024
Abstract
Tissue-resident
innate
immune
cells
have
important
functions
in
both
homeostasis
and
pathological
states.
Despite
advances
the
field,
analyzing
metabolism
of
tissue-resident
lymphocytes
is
still
challenging.
The
small
number
such
as
ILC,
NK,
iNKT
γδ
T
poses
additional
obstacles
their
metabolic
studies.
In
this
review,
we
summarize
current
understanding
lymphocyte
discuss
potential
pitfalls
associated
with
methodology
relying
predominantly
on
vitro
cultured
or
bulk-level
comparison.
Meanwhile,
also
advocate
for
development
adoption
single-cell
assays
to
accurately
profile
directly
ex
vivo.
Current Opinion in Immunology,
Год журнала:
2024,
Номер
91, С. 102487 - 102487
Опубликована: Сен. 21, 2024
A
simple
definition
of
life
is
a
system
that
can
self-replicate
(proliferation)
and
self-sustain
(metabolism).
At
the
cellular
level,
metabolism
has
evolved
to
drive
proliferation,
which
requires
energy
building
blocks
duplicate
biomass
before
division.
T
lymphocytes
(or
cells)
are
required
for
adaptive
immune
responses,
protecting
us
against
invading
malignant
agents
capable
hyper-replication.
To
gain
competitive
advantage
over
these
agents,
activated
cells
their
divide
into
two
daughter
in
as
short
2-6
hours,
considered
fastest
cell
division
among
all
types
vertebrates.
Thus,
primary
task
commit
available
resources
hyperproliferation.
Beyond
that,
cycle
involves
an
ordered
series
fate-determining
events
transition
between
discrete
states.
stages
not
involved
hyperproliferation,
engage
metabolic
programs
more
flexible
sustain
viability
maintenance
sometimes
fine-tuned
support
specific
activities.
Here,
we
focus
on
central
carbon
metabolism,
most
relevant
proliferation.
We
provide
examples
how
changes
may
or
change
fate
further
explore
few
conceptual
frameworks,
such
flexibility,
Goldilocks
Principle,
overflow
effector-signaling
metabolites,
context
transitions.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 29, 2024
Chimeric
antigen
receptor
T
cell
(CART)
therapy
has
seen
great
clinical
success.
However,
up
to
50%
of
leukemia
patients
relapse
and
long-term
survivor
data
indicate
that
CART
persistence
is
key
enforcing
relapse-free
survival.
Unfortunately,
ex
vivo
expansion
protocols
often
drive
metabolic
functional
exhaustion,
reducing
in
efficacy.
Preclinical
models
have
demonstrated
redirecting
metabolism
can
improve
function
we
hypothesized
exposure
an
agonist
targeting
the
regulator
AMP-activated
protein
kinase
(AMPK),
would
create
CARTs
capable
both
efficient
clearance
increased
persistence.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 14, 2024
SUMMARY
Glucose
is
essential
for
T
cell
proliferation
and
function,
yet
its
specific
metabolic
roles
in
vivo
remain
poorly
defined.
Here,
we
identify
glycosphingolipid
(GSL)
biosynthesis
as
a
key
pathway
fueled
by
glucose
that
enables
CD8
+
expansion
cytotoxic
function
.
Using
13
C-based
stable
isotope
tracing,
demonstrate
effector
cells
use
to
synthesize
uridine
diphosphate-glucose
(UDP-Glc),
precursor
glycogen,
glycan,
GSL
biosynthesis.
Inhibiting
production
targeting
the
enzymes
UGP2
or
UGCG
impairs
cytolytic
activity
without
affecting
glucose-dependent
energy
production.
Mechanistically,
show
required
plasma
membrane
lipid
raft
integrity
aggregation
following
TCR
stimulation.
Moreover,
UGCG-deficient
display
reduced
granzyme
expression
tumor
control
Together,
our
data
establish
critical
fate
of
glucose—independent
production—required
responses
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 15, 2024
Reducing
calorie
intake
without
malnutrition
limits
tumor
progression
but
the
underlying
mechanisms
are
poorly
understood.
Here
we
show
that
dietary
restriction
(DR)
suppresses
growth
by
enhancing
CD8
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 30, 2024
Abstract
Tissue-resident
innate
immune
cells
have
important
functions
in
both
homeostasis
and
pathological
states.
Despite
advances
the
field,
analyzing
metabolism
of
tissue-resident
lymphocytes
is
still
challenging.
The
small
number
such
as
ILC,
NK,
iNKT
γδ
T
poses
additional
obstacles
their
metabolic
studies.
In
this
review,
we
summarize
current
understanding
lymphocyte
discuss
potential
pitfalls
associated
with
methodology
relying
predominantly
on
vitro
cultured
or
bulk-level
comparison.
Meanwhile,
also
advocate
for
development
adoption
single-cell
assays
to
accurately
profile
directly
ex
vivo.
