bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 15, 2023
How
to
identify
true
biological
differences
across
samples
while
overcoming
batch
effects
has
been
a
persistent
challenge
in
single-cell
RNA-seq
data
analysis,
hindering
analyses
datasets
for
transferable
findings.
In
this
work,
we
show
that
scaling
up
deep
identifiable
models
leads
surprisingly
effective
solution
challenging
task.
We
developed
scShift,
variational
inference
framework
with
theoretical
support
disentangling
batch-dependent
and
independent
variations.
By
training
the
model
compendiums
of
scRNA-seq
atlases,
scShift
shows
remarkable
zero-shot
capabilities
revealing
representations
cell
types
states
effects.
employed
systematically
compare
lung
fibrosis
different
datasets,
tissues
experimental
systems.
uniquely
extrapolates
previously
unseen
post-COVID-19
fibrosis,
characterizing
universal
myeloid-fibrosis
signatures,
potential
repurposing
drug
targets
fibrosis-associated
interactions.
Evaluations
over
200
trained
demonstrate
emergent
law
beyond
transition
threshold,
respect
dataset
diversity.
With
its
performance
on
massive
exceptional
capabilities,
represents
an
important
advance
toward
next-generation
computational
analysis.
AJP Cell Physiology,
Год журнала:
2023,
Номер
325(4), С. C1046 - C1057
Опубликована: Сен. 11, 2023
Pulmonary
fibrosis
results
from
a
plethora
of
abnormal
pathogenetic
events.
In
idiopathic
pulmonary
(IPF),
inhalational,
environmental,
or
occupational
exposures
in
genetically
and
epigenetically
predisposed
individuals
trigger
recurrent
cycles
alveolar
epithelial
cell
injury,
activation
coagulation
pathways,
chemoattraction,
differentiation
monocytes
into
monocyte-derived
macrophages
(Mo-AMs).
When
these
events
happen
intermittently
repeatedly
throughout
the
individual's
life
cycle,
wound
repair
process
becomes
aberrant
leading
to
bronchiolization
distal
air
spaces,
fibroblast
accumulation,
extracellular
matrix
deposition,
loss
alveolar-capillary
architecture.
The
role
immune
dysregulation
IPF
pathogenesis
progression
has
been
underscored
past
mainly
after
disappointing
immunosuppressant
use
patients;
however,
recent
reports
highlighting
prognostic
mechanistic
roles
Mo-AMs
revived
interest
IPF.
this
review,
we
will
discuss
cells
onset
IPF,
as
well
potential
targeted
therapies.
American Journal of Respiratory and Critical Care Medicine,
Год журнала:
2024,
Номер
210(4), С. 401 - 423
Опубликована: Апрель 4, 2024
Recent
genetic
and
genomic
advancements
have
elucidated
the
complex
etiology
of
idiopathic
pulmonary
fibrosis
(IPF)
other
progressive
fibrotic
interstitial
lung
diseases
(ILDs),
emphasizing
contribution
heritable
factors.
This
state-of-the-art
review
synthesizes
evidence
on
significant
contributors
to
(PF),
including
rare
variants
common
single
nucleotide
polymorphisms
(SNPs).
The
MUC5B
promoter
variant
is
unusual,
a
SNP
that
markedly
elevates
risk
early
established
PF.
We
address
utility
variation
in
enhancing
understanding
disease
pathogenesis,
clinical
phenotypes,
improving
definitions,
informing
prognosis
treatment
response.
Critical
research
gaps
are
highlighted,
particularly
underrepresentation
non-European
ancestries
PF
studies
exploration
phenotypes
beyond
usual
pneumonia
(UIP)/IPF.
discuss
role
telomere
length,
often
critically
short
PF,
its
link
progression
mortality,
underscoring
complexity
involving
biology
genes
(TERT,
TERC)
others
like
SFTPC
MUC5B.
Additionally,
we
potential
gene-by-environment
interactions
modulate
manifestation,
advocating
for
precision
medicine
Insights
from
gene
expression
profiling
multi-omic
analyses
highlight
promise
pathogenesis
offer
new
approaches
care,
therapeutic
drug
development,
biomarker
discovery.
Finally,
ethical,
legal,
social
implications
therapies
stressing
need
sound
practices
informed
discussions.
Looking
forward,
advocate
comprehensive
testing
panels
polygenic
scores
improve
management
related
ILDs
across
diverse
populations.
Breathe,
Год журнала:
2025,
Номер
21(2), С. 240167 - 240167
Опубликована: Апрель 1, 2025
Interstitial
lung
disease
(ILD)
is
a
heterogeneous
chronic
form
of
disease.
The
pathogenesis
ILD
poorly
understood
and
common
ILD,
idiopathic
pulmonary
fibrosis
(IPF)
associated
with
poor
prognosis.
There
evidence
for
substantial
dysregulated
immune
responses
in
ILD.
microbiome
key
regulator
the
response,
correlates
alveolar
immunity
clinical
outcomes
Most
observational
studies
have
been
conducted
patients
IPF.
A
consistent
observation
these
that
bacterial
burden
elevated
IPF
predicts
mortality.
However,
our
understanding
mechanism
incomplete
role
other
forms
limited.
microbiomes
oropharynx
gut
may
implications
but
require
further
research.
Here,
we
discuss
supporting
IPF,
briefly
describe
putative
oral–lung
axis
gut–lung
AJP Cell Physiology,
Год журнала:
2024,
Номер
326(3), С. C964 - C977
Опубликована: Янв. 8, 2024
MCEMP1
is
highly
expressed
in
circulating
classical
monocytes
and
alveolar
macrophages
IPF,
regulated
by
TGFβ,
participates
the
chemotaxis,
adhesion,
migration
of
modulating
effect
TGFβ
RHO
activity.
European Respiratory Review,
Год журнала:
2023,
Номер
32(169), С. 230072 - 230072
Опубликована: Сен. 6, 2023
Peripheral
blood
monocyte
counts
have
been
associated
with
poor
outcomes
in
interstitial
lung
disease
(ILD).
However,
studies
are
limited
by
variable
biomarker
thresholds,
analytic
approaches
and
heterogenous
populations.
This
systematic
review
meta-analysis
characterised
the
relationship
between
monocytes
clinical
ILD.
Deleted Journal,
Год журнала:
2025,
Номер
3(1), С. 10004 - 10004
Опубликована: Янв. 1, 2025
Idiopathic
pulmonary
fibrosis
(IPF)
is
marked
by
progressive
alveolar
destruction,
impaired
tissue
regeneration,
and
relentless
fibrogenesis,
culminating
in
respiratory
failure
death.
A
diverse
array
of
resident
non-resident
cells
within
the
lung
contribute
to
disease
pathogenesis.
Notably,
immune
cells,
both
recruited,
respond
cues
from
sites
injury
undergoing
phenotypic
transitions
producing
a
wide
range
mediators
that
influence,
initiate,
or
dictate
function,
dysfunction,
key
effector
IPF
pathology,
such
as
epithelial
fibroblasts,
capillary
endothelial
cells.
The
role
system
has
undergone
an
interesting
evolution,
oscillating
initial
enthusiasm
skepticism,
now
renewed
focus.
This
shift
reflects
past
failures
immune-targeting
therapies
for
unprecedented
insights
into
cell
heterogeneity
provided
emerging
technologies.
In
this
article,
we
review
historical
evolution
perspectives
on
system's
pathogenesis
examine
lessons
learned
previous
therapeutic
targeting
responses.
We
discuss
major
types
implicated
progression,
highlighting
their
mechanisms
action.
Finally,
identify
knowledge
gaps
propose
future
directions
research
IPF.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 20, 2025
The
airway
epithelial
barrier
is
the
first
defence
against
aeroallergens.
Nasal
cells
(NECs)
are
vital
in
regulating
innate
and
adaptive
mucosal
immunity
allergic
rhinitis
(AR).
Tregs
produce
cytokines
essential
for
immunomodulatory
activities
allergen
immunotherapy.
Understanding
relationship
between
NECs
hyperresponsiveness
network
developing
novel
treatments.
Using
an
vitro
human
Treg-NEC
co-culture
system
of
AR
health
control
group,
chemokine
expression
profiles
were
examined
using
immunohistochemistry,
RT-PCR,
ELISA,
functional
surface
markers
detected
flow
cytometric
analysis.
Correlation
analysis
was
performed
derived
from
CD4+CD8+Foxp3+
group
after
co-culture,
including
TSLP/CTLA4,
CCL1/CTLA4,
TSLP/CCR8,
CCL1/CCR8.
CCR8
CTLA-4
expressions
co-culturing
higher
than
single
culture.
Following
Derp1
stimulation,
TSLP,
IL-25
TGF-β
+
increased.
CCL1
mRNA
lower
group.
In
TSLP
higher,
protein
levels
decreased.
There
no
significant
differences
IL-25,
IL-10.
When
Treg
added,
changes
similar
to
that
observed
pNECs.
After
CCL1/CCR8
positively
correlated
AR.
Human
pNECs
can
communicate
with
directly,
may
be
pathway
play
a
key
role
immune
