Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Авг. 22, 2024
Crohn's
disease
(CD)
is
a
complex
chronic
inflammatory
disorder
with
both
gastrointestinal
and
extra-intestinal
manifestations
associated
immune
dysregulation.
Analyzing
202,359
cells
from
170
specimens
across
83
patients,
we
identify
distinct
epithelial
cell
type
in
terminal
ileum
ascending
colon
(hereon
as
'LND')
high
expression
of
LCN2,
NOS2,
DUOX2
genes
related
to
antimicrobial
response
immunoregulation.
LND
cells,
confirmed
by
in-situ
RNA
protein
imaging,
are
rare
non-IBD
controls
but
expand
active
CD,
actively
interact
specifically
express
IBD/CD
susceptibility
genes,
suggesting
possible
function
CD
immunopathogenesis.
Furthermore,
discover
early
late
subpopulations
different
origins
developmental
potential.
A
higher
ratio
late-to-early
correlates
better
anti-TNF
treatment.
Our
findings
thus
suggest
potential
pathogenic
role
for
ileitis
colitis.
Here
the
authors
use
multimodal
data
characterize
an
population,
termed
'LND'
colon,
interacting
locally
potentially
contributing
pathology.
Nature Immunology,
Год журнала:
2023,
Номер
24(9), С. 1540 - 1551
Опубликована: Авг. 10, 2023
Circulating
proteins
have
important
functions
in
inflammation
and
a
broad
range
of
diseases.
To
identify
genetic
influences
on
inflammation-related
proteins,
we
conducted
genome-wide
protein
quantitative
trait
locus
(pQTL)
study
91
plasma
measured
using
the
Olink
Target
platform
14,824
participants.
We
identified
180
pQTLs
(59
cis,
121
trans).
Integration
pQTL
data
with
eQTL
disease
association
studies
provided
insight
into
pathogenesis,
implicating
lymphotoxin-α
multiple
sclerosis.
Using
Mendelian
randomization
(MR)
to
assess
causality
etiology,
both
shared
distinct
effects
specific
across
immune-mediated
diseases,
including
directionally
discordant
CD40
risk
rheumatoid
arthritis
versus
sclerosis
inflammatory
bowel
disease.
MR
implicated
CXCL5
etiology
ulcerative
colitis
(UC)
show
elevated
gut
transcript
expression
patients
UC.
These
results
targets
existing
drugs
provide
powerful
resource
facilitate
future
drug
target
prioritization.
Med,
Год журнала:
2022,
Номер
3(7), С. 481 - 518.e14
Опубликована: Май 31, 2022
Pro-inflammatory
fibroblasts
are
critical
for
pathogenesis
in
rheumatoid
arthritis,
inflammatory
bowel
disease,
interstitial
lung
and
Sjögren's
syndrome
represent
a
novel
therapeutic
target
chronic
disease.
However,
the
heterogeneity
of
fibroblast
phenotypes,
exacerbated
by
lack
common
cross-tissue
taxonomy,
has
limited
our
understanding
which
pathways
shared
multiple
diseases.
Nature Immunology,
Год журнала:
2023,
Номер
24(7), С. 1200 - 1210
Опубликована: Июнь 5, 2023
Abstract
Inflammation
of
non-barrier
immunologically
quiescent
tissues
is
associated
with
a
massive
influx
blood-borne
innate
and
adaptive
immune
cells.
Cues
from
the
latter
are
likely
to
alter
expand
activated
states
resident
However,
local
communications
between
immigrant
cell
types
in
human
inflammatory
disease
remain
poorly
understood.
Here,
we
explored
drivers
fibroblast-like
synoviocyte
(FLS)
heterogeneity
inflamed
joints
patients
rheumatoid
arthritis
using
paired
single-cell
RNA
ATAC
sequencing,
multiplexed
imaging
spatial
transcriptomics
along
vitro
modeling
cell-extrinsic
factor
signaling.
These
analyses
suggest
that
exposures
myeloid
T
cell-derived
cytokines,
TNF,
IFN-γ,
IL-1β
or
lack
thereof,
drive
four
distinct
FLS
some
which
closely
resemble
fibroblast
other
disease-affected
including
skin
colon.
Our
results
highlight
role
for
concurrent,
spatially
distributed
cytokine
signaling
within
synovium.
Cancers,
Год журнала:
2023,
Номер
15(5), С. 1629 - 1629
Опубликована: Март 6, 2023
Immune-checkpoint
inhibitors
(ICIs)
are
antagonists
of
inhibitory
receptors
in
the
immune
system,
such
as
cytotoxic
T-lymphocyte-associated
antigen-4,
programmed
cell
death
protein-1
and
its
ligand
PD-L1,
they
increasingly
used
cancer
treatment.
By
blocking
certain
suppressive
pathways,
ICIs
promote
T-cell
activation
antitumor
activity
but
may
induce
so-called
immune-related
adverse
events
(irAEs),
which
mimic
traditional
autoimmune
disorders.
With
approval
more
ICIs,
irAE
prediction
has
become
a
key
factor
improving
patient
survival
quality
life.
Several
biomarkers
have
been
described
potential
predictors,
some
them
already
available
for
clinical
use
others
under
development;
examples
include
circulating
blood
counts
ratios,
expansion
diversification,
cytokines,
autoantibodies
autoantigens,
serum
other
biological
fluid
proteins,
human
leucocyte
antigen
genotypes,
genetic
variations
gene
profiles,
microRNAs,
gastrointestinal
microbiome.
Nevertheless,
it
is
difficult
to
generalize
application
based
on
current
evidence
because
most
studies
retrospective,
time-limited
restricted
specific
type
cancer,
or
ICI.
Long-term
prospective
cohorts
real-life
needed
assess
predictive
capacity
different
biomarkers,
regardless
ICI
type,
organ
involved
site.
