European Journal of Immunology,
Год журнала:
2022,
Номер
52(7), С. 1129 - 1140
Опубликована: Апрель 13, 2022
Mesenchymal
stromal
cells
(MSCs)
are
well
known
for
their
immunoregulatory
roles
on
allergic
inflammation
particularly
by
acting
T
cells,
B
and
dendritic
(DCs).
MSC-derived
small
extracellular
vesicles
(MSC-sEV)
increasingly
considered
as
one
of
the
main
factors
effects
MSCs
immune
responses.
However,
MSC-sEV
DCs
in
diseases
remain
unclear.
were
prepared
from
induced
pluripotent
stem
(iPSC)-MSCs
anion-exchange
chromatography,
characterized
with
size,
morphology,
specific
markers.
Human
monocyte-derived
generated
cultured
presence
to
differentiate
so-called
sEV-immature
(sEV-iDCs)
sEV-mature
(sEV-mDCs),
respectively.
The
phenotypes
phagocytic
ability
sEV-iDCs
analyzed
flow
cytometry.
sEV-mDCs
co-cultured
isolated
CD4+
or
peripheral
blood
mononuclear
(PBMCs)
patients
rhinitis.
levels
Th1
Th2
cytokines
produced
examined
ELISA
intracellular
staining.
And
following
mechanisms
further
investigated.
We
demonstrated
that
inhibited
differentiation
human
monocytes
iDCs
downregulation
expression
CD40,
CD80,
CD86,
HLA-DR,
but
had
no
mDCs
these
treatment
enhanced
mDCs.
More
importantly,
using
anti-IL-10
monoclonal
antibody
IL-10Rα
blocking
antibody,
we
identified
suppressed
response
reducing
production
IL-4,
IL-9,
IL-13
via
IL-10.
Furthermore,
increased
level
Treg
cells.
Our
study
treated
responses,
providing
novel
evidence
potential
cell-free
therapy
airway
diseases.
Nature Immunology,
Год журнала:
2022,
Номер
23(11), С. 1551 - 1563
Опубликована: Окт. 26, 2022
Clonal
expansion
of
cells
with
somatically
diversified
receptors
and
their
long-term
maintenance
as
memory
is
a
hallmark
adaptive
immunity.
Here,
we
studied
pathogen-specific
adaptation
within
the
innate
immune
system,
tracking
natural
killer
(NK)
cell
to
human
cytomegalovirus
(HCMV)
infection.
Leveraging
single-cell
multiomic
maps
ex
vivo
NK
somatic
mitochondrial
DNA
mutations
endogenous
barcodes,
reveal
substantial
clonal
in
HCMV
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Июнь 10, 2022
Several
COVID-19
convalescents
suffer
from
the
post-acute
COVID-syndrome
(PACS)/long
COVID,
with
symptoms
that
include
fatigue,
dyspnea,
pulmonary
fibrosis,
cognitive
dysfunctions
or
even
stroke.
Given
scale
of
worldwide
infections,
long-term
recovery
and
integrative
health-care
in
nearest
future,
it
is
critical
to
understand
cellular
molecular
mechanisms
as
well
possible
predictors
longitudinal
post-COVID-19
responses
convalescent
individuals.
The
immune
system
T
cell
alterations
are
proposed
drivers
COVID
syndrome.
However,
despite
number
studies
on
COVID-19,
many
them
addressed
only
severe
short-term
responses.
Here,
we
performed
mild,
moderate
COVID-19-convalescent
patients,
at
two
time
points
(3
6
months
infection),
assess
dynamics
cells
landscape,
integrated
patients-reported
symptoms.
We
show
among
subsets
exhibit
different,
severity-
time-dependent
dynamics,
result
a
polarization
towards
an
exhausted/senescent
state
CD4+
CD8+
perturbances
Tregs.
In
particular,
high
proportion
CD57+
terminal
effector
cells,
together
significant
decrease
naïve
population,
augmented
granzyme
B
IFN-γ
production
unresolved
inflammation
after
infection.
Mild
showed
increased
naïve,
decreased
central
memory
Treg
subsets.
Patients
all
severity
groups
can
be
predisposed
long
symptoms,
fatigue
not
necessarily
related
dysfunctions,
was
found
convalescents.
conclusion,
functional
remodeling
could
seen
two-step
process,
leading
distinct
states
Our
data
imply
attenuation
blocking
might
influence
post-COVID
either
search
for
any
treatment
prevent
PACS
further
complications
mandatory
patients
SARS-CoV-2
infection,
those
suffering
COVID-19.
Nature,
Год журнала:
2022,
Номер
605(7911), С. 728 - 735
Опубликована: Май 11, 2022
Abstract
Immunotherapies
have
achieved
remarkable
successes
in
the
treatment
of
cancer,
but
major
challenges
remain
1,2
.
An
inherent
weakness
current
approaches
is
that
therapeutically
targeted
pathways
are
not
restricted
to
tumours,
also
found
other
tissue
microenvironments,
complicating
3,4
Despite
great
efforts
define
inflammatory
processes
tumour
microenvironment,
understanding
tumour-unique
immune
alterations
limited
by
a
knowledge
gap
regarding
cell
populations
inflamed
human
tissues.
Here,
an
effort
identify
such
tumour-enriched
alterations,
we
used
complementary
single-cell
analysis
interrogate
infiltrate
head
and
neck
squamous
carcinomas
site-matched
non-malignant,
Our
revealed
large
overlap
composition
phenotype
cells
Computational
identified
interactions,
one
which
yields
population
regulatory
T
(T
reg
)
highly
enriched
uniquely
among
all
haematopoietically-derived
blood
co-expression
ICOS
IL-1
receptor
type
1
(IL1R1).
We
provide
evidence
these
intratumoural
IL1R1
+
had
responded
antigen
recently
demonstrate
they
clonally
expanded
with
superior
suppressive
function
compared
−
cells.
In
addition
identifying
extensive
immunological
congruence
between
tissues
tumours
as
well
tumour-specific
changes
direct
disease
relevance,
our
work
provides
blueprint
for
extricating
disease-specific
from
general
inflammation-associated
patterns.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 26, 2024
Abstract
The
tumor
microenvironment
(TME)
constitutes
a
complex
comprising
diverse
array
of
immune
cells
and
stromal
components.
Within
this
intricate
context,
tumor-associated
macrophages
(TAMs)
exhibit
notable
spatial
heterogeneity.
This
heterogeneity
contributes
to
various
facets
behavior,
including
response
modulation,
angiogenesis,
tissue
remodeling,
metastatic
potential.
review
summarizes
the
distribution
in
both
physiological
environment
TME.
Moreover,
paper
explores
interactions
between
TAMs
cell
populations
(T
cells,
dendritic
neutrophils,
natural
killer
other
cells)
within
These
bidirectional
exchanges
form
network
that
influence
surveillance
evasion
strategies.
Investigating
TAM
its
with
different
offers
potential
avenues
for
therapeutic
interventions.
Additionally,
discusses
strategies
targeting
macrophages,
aiming
uncover
novel
approaches
immunotherapy.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 13, 2024
Abstract
T
cells
have
the
ability
to
eliminate
infected
and
cancer
play
an
essential
role
in
immunotherapy.
cell
activation
is
elicited
by
binding
of
receptor
(TCR)
epitopes
displayed
on
MHC
molecules,
TCR
specificity
determined
sequence
its
α
β
chains.
Here,
we
collect
curate
a
dataset
17,715
αβTCRs
interacting
with
dozens
class
I
II
epitopes.
We
use
this
curated
data
develop
MixTCRpred,
epitope-specific
TCR-epitope
interaction
predictor.
MixTCRpred
accurately
predicts
TCRs
recognizing
several
viral
further
provides
useful
quality
control
tool
for
multiplexed
single-cell
sequencing
assays
pinpoints
substantial
fraction
putative
contaminants
public
databases.
Analysis
dual
demonstrates
that
can
identify
chains
mediating
epitope
recognition.
Applying
repertoires
from
COVID-19
patients
reveals
enrichment
clonotypes
predicted
bind
immunodominant
SARS-CoV-2
epitope.
Overall,
robust
predict
specific
interpret
TCR-sequencing
both
bulk
cells.
Arteriosclerosis Thrombosis and Vascular Biology,
Год журнала:
2024,
Номер
44(4), С. 930 - 945
Опубликована: Фев. 22, 2024
BACKGROUND:
Atherosclerotic
plaques
are
complex
tissues
composed
of
a
heterogeneous
mixture
cells.
However,
our
understanding
the
comprehensive
transcriptional
and
phenotypic
landscape
cells
within
these
lesions
is
limited.
METHODS:
To
characterize
human
carotid
atherosclerosis
in
greater
detail,
we
combined
cellular
indexing
transcriptomes
epitopes
by
sequencing
single-cell
RNA
to
classify
all
cell
types
(n=21;
13
symptomatic)
achieve
multimodal
identities
their
association
with
clinical
pathophysiology.
RESULTS:
We
identified
25
populations,
each
unique
multiomic
signature,
including
macrophages,
T
cells,
NK
(natural
killer)
mast
B
plasma
neutrophils,
dendritic
endothelial
fibroblasts,
smooth
muscle
(SMCs).
Among
2
proinflammatory
subsets
enriched
IL-1B
(interleukin-1B)
or
C1Q
expression,
TREM2-positive
foam
(1
expressing
inflammatory
genes),
subpopulations
proliferative
gene
signature
SMC-specific
fibrotic
pathways
upregulated.
Further
characterization
revealed
various
SMCs
SMC-derived
These
foamy
were
localized
deep
intima
coronary
atherosclerotic
lesions.
Utilizing
data,
developed
flow
cytometry
panel,
using
surface
proteins
CD29,
CD142,
CD90,
isolate
from
Lastly,
observed
reduced
proportions
efferocytotic
classically
activated
contractile
modulated
while
clinically
symptomatic
versus
asymptomatic
patients.
CONCLUSIONS:
Our
atlas
populations
provides
novel
insights
into
diversity,
phenotype,
location,
isolation,
relevance
composition
atherosclerosis.
findings
facilitate
both
mapping
cardiovascular
disease
susceptibility
loci
specific
identification
molecular
therapeutic
targets
for
treatment
disease.
Cytometry Part A,
Год журнала:
2024,
Номер
105(6), С. 430 - 436
Опубликована: Апрель 18, 2024
Abstract
We
report
the
development
of
an
optimized
50‐color
spectral
flow
cytometry
panel
designed
for
in‐depth
analysis
immune
system
in
human
blood
and
tissues,
with
goal
maximizing
amount
information
that
can
be
collected
using
currently
available
platforms.
established
tested
this
peripheral
mononuclear
cells
(PBMCs),
but
included
CD45
to
enable
its
future
use
tissue
samples.
The
contains
lineage
markers
all
major
cell
subsets,
extensive
set
phenotyping
focused
on
activation
differentiation
status
T
dendritic
(DC)
compartment.
outline
biological
insight
gained
from
simultaneous
measurement
such
a
large
number
proteins
propose
approach
provides
unique
opportunity
comprehensive
exploration
samples
limited
cells.
Of
note,
we
compatible
sorting
further
downstream
applications.
Furthermore,
facilitate
wide‐spread
implementation
across
different
cohorts
samples,
trimmed‐down
45‐color
version
which
used
Finally,
generate
panel,
utilized
not
only
existing
design
guidelines,
also
developed
new
metrics
systematically
identify
optimal
combination
50
fluorochromes
evaluate
fluorochrome‐specific
resolution
context
unmixing
matrix.
