Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 26, 2023
Abstract
Ulcerative
colitis
and
Crohn’s
disease
are
chronic
inflammatory
intestinal
diseases
with
perplexing
heterogeneity
in
manifestation
response
to
treatment.
While
the
molecular
basis
for
this
remains
uncharacterized,
single-cell
technologies
allow
us
explore
transcriptional
states
within
tissues
at
an
unprecedented
resolution
which
could
further
understanding
of
these
complex
diseases.
Here,
we
apply
RNA-sequencing
human
inflamed
intestine
show
that
largest
differences
among
patients
present
myeloid
compartment
including
macrophages
neutrophils.
Using
spatial
transcriptomics
tissue
(CosMx
Spatial
Molecular
Imaging)
spatially
localize
each
macrophage
neutrophil
subsets
identified
by
unravel
diversity
based
on
their
localization.
Finally,
combined
analysis
reveals
a
strong
communication
network
involving
fibroblasts.
Our
data
sheds
light
cellular
complexity
points
towards
stromal
compartments
as
important
patient-to-patient
heterogeneity.
Immunity,
Год журнала:
2023,
Номер
56(10), С. 2188 - 2205
Опубликована: Окт. 1, 2023
The
cancer-immunity
cycle
provides
a
framework
to
understand
the
series
of
events
that
generate
anti-cancer
immune
responses.
It
emphasizes
iterative
nature
response
where
killing
tumor
cells
by
T
initiates
subsequent
rounds
antigen
presentation
and
cell
stimulation,
maintaining
active
immunity
adapting
it
evolution.
Any
step
can
become
rate-limiting,
rendering
system
unable
control
growth.
Here,
we
update
based
on
remarkable
progress
past
decade.
Understanding
mechanism
checkpoint
inhibition
has
evolved,
as
our
view
dendritic
in
sustaining
anti-tumor
immunity.
We
additionally
account
for
role
microenvironment
facilitating,
not
just
suppressing,
response,
discuss
importance
considering
tumor's
immunological
phenotype,
"immunotype".
While
these
new
insights
add
some
complexity
cycle,
they
also
provide
targets
research
therapeutic
intervention.
Science Immunology,
Год журнала:
2022,
Номер
7(67)
Опубликована: Янв. 7, 2022
Resident
macrophages
orchestrate
homeostatic,
inflammatory,
and
reparative
activities.
It
is
appreciated
that
different
tissues
instruct
specialized
macrophage
functions.
However,
individual
contain
heterogeneous
subpopulations,
how
these
subpopulations
are
related
unclear.
We
asked
whether
common
transcriptional
functional
elements
could
reveal
an
underlying
framework
across
tissues.
Using
single-cell
RNA
sequencing
random
forest
modeling,
we
observed
four
genes
predict
three
subsets
were
present
in
murine
heart,
liver,
lung,
kidney,
brain.
Parabiotic
genetic
fate
mapping
studies
revealed
core
markers
predicted
unique
life
cycles
17
TLF+
(expressing
TIMD4
and/or
LYVE1
FOLR2)
maintained
through
self-renewal
with
minimal
monocyte
input;
CCR2+
(TIMD4−LYVE1−FOLR2−)
almost
entirely
replaced
by
monocytes,
MHC-IIhi
(TIMD4−LYVE1−FOLR2−CCR2−),
while
receiving
modest
contribution,
not
continually
replaced.
Rather,
monocyte-derived
contributed
to
the
resident
population
until
they
reached
a
defined
upper
limit
after
which
did
outcompete
pre-existing
macrophages.
Developmentally,
first
emerge
yolk
sac
early
fetal
organs.
Fate
mouse
human
indicated
originated
from
both
precursors.
Furthermore,
most
transcriptionally
conserved
subset
between
mice
humans,
despite
organ-
species-specific
differences.
Here,
define
existence
of
based
on
cycle
properties
gene
signatures
provide
starting
point
understand
tissue
heterogeneity.
Nature reviews. Immunology,
Год журнала:
2023,
Номер
23(9), С. 563 - 579
Опубликована: Март 15, 2023
Macrophages
are
innate
immune
cells
that
form
a
3D
network
in
all
our
tissues,
where
they
phagocytose
dying
and
cell
debris,
complexes,
bacteria
other
waste
products.
Simultaneously,
produce
growth
factors
signalling
molecules
—
such
activities
not
only
promote
host
protection
response
to
invading
microorganisms
but
also
crucial
for
organ
development
homeostasis.
There
is
mounting
evidence
of
macrophages
orchestrating
fundamental
physiological
processes,
as
blood
vessel
formation,
adipogenesis,
metabolism
central
peripheral
neuronal
function.
In
parallel,
novel
methodologies
have
led
the
characterization
tissue-specific
macrophages,
with
distinct
subpopulations
these
showing
different
developmental
trajectories,
transcriptional
programmes
life
cycles.
Here,
we
summarize
growing
knowledge
macrophage
diversity
how
subsets
orchestrate
tissue
We
further
interrelate
ontogeny
their
core
functions
across
is,
events
within
niche
may
control
functionality
during
development,
homeostasis
ageing.
Finally,
highlight
open
questions
will
need
be
addressed
by
future
studies
better
understand
subsets.
important
immunity
infections
clearing
products
from
maintain
health
regulating
metabolism,
many
biological
processes.
Elvira
Mass
co-workers
discuss
populations
found
throughout
body,
highlighting
shared
unique
aspects
functions.
Cellular and Molecular Immunology,
Год журнала:
2023,
Номер
20(5), С. 432 - 447
Опубликована: Март 22, 2023
Abstract
Dendritic
cells
(DCs)
exhibit
a
specialized
antigen-presenting
function
and
play
crucial
roles
in
both
innate
adaptive
immune
responses.
Due
to
their
ability
cross-present
tumor
cell-associated
antigens
naïve
T
cells,
DCs
are
instrumental
the
generation
of
specific
T-cell-mediated
antitumor
effector
responses
control
growth
cell
dissemination.
Within
an
immunosuppressive
microenvironment,
DC
functions
can,
however,
be
severely
impaired.
In
this
review,
we
focus
on
mechanisms
capture
activation
by
role
microenvironment
shaping
functions,
taking
advantage
recent
studies
showing
phenotype
acquisition,
transcriptional
state
functional
programs
revealed
scRNA-seq
analysis.
The
therapeutic
potential
DC-mediated
antigen
sensing
priming
immunity
is
also
discussed.