Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: July 29, 2022
Osteoarthritis
(OA)
is
the
most
common
joint
disease,
affecting
over
300
million
people
world-wide.
Accumulating
evidence
attests
to
important
roles
of
immune
system
in
OA
pathogenesis.
Understanding
role
various
cells
degeneration
or
repair
after
injury
vital
for
improving
therapeutic
strategies
treating
OA.
Post-traumatic
osteoarthritis
(PTOA)
develops
~50%
individuals
who
have
experienced
an
articular
trauma
like
anterior
cruciate
ligament
(ACL)
rupture.
Here,
using
high
resolution
single-cell
RNA
sequencing,
we
delineated
temporal
dynamics
cell
accumulation
mouse
knee
ACL
Our
study
identified
multiple
types
including
neutrophils,
monocytes,
macrophages,
B
cells,
T
NK
and
dendritic
cells.
Monocytes
macrophage
populations
showed
dramatic
changes
injury.
Further
characterization
monocytes
macrophages
reveled
9
major
subtypes
with
unique
transcriptomics
signatures,
a
tissue
resident
Lyve1
hi
Folr2
population
Trem2
Fcrls
+
recruited
both
showing
enrichment
phagocytic
genes
growth
factors
such
as
Igf1
,
Pdgfa
Pdgfc.
We
also
several
induced
repressed
type-specific
manner.
This
provides
new
insight
into
PTOA-associated
microenvironment
highlights
that
may
play
Science Immunology,
Journal Year:
2023,
Volume and Issue:
8(82)
Published: April 7, 2023
Macrophages
are
central
orchestrators
of
the
tissue
response
to
injury,
with
distinct
macrophage
activation
states
playing
key
roles
in
fibrosis
progression
and
resolution.
Identifying
populations
found
human
fibrotic
tissues
could
lead
new
treatments
for
fibrosis.
Here,
we
used
liver
lung
single-cell
RNA
sequencing
datasets
identify
a
subset
CD9+TREM2+
macrophages
that
express
SPP1,
GPNMB,
FABP5,
CD63.
In
both
murine
hepatic
pulmonary
fibrosis,
these
were
enriched
at
outside
edges
scarring
adjacent
activated
mesenchymal
cells.
Neutrophils
expressing
MMP9,
which
participates
TGF-β1,
type
3
cytokines
GM-CSF
IL-17A
coclustered
macrophages.
vitro,
GM-CSF,
IL-17A,
TGF-β1
drive
differentiation
monocytes
into
scar-associated
markers.
Such
differentiated
cells
degrade
collagen
IV
but
not
I
promote
TGF-β1-induced
deposition
by
models
blocking
or
reduced
expansion
Our
work
identifies
highly
specific
population
assign
profibrotic
role
across
species
tissues.
It
further
provides
strategy
unbiased
discovery,
triage,
preclinical
validation
therapeutic
targets
based
on
this
fibrogenic
population.
Molecular Neurodegeneration,
Journal Year:
2022,
Volume and Issue:
17(1)
Published: June 3, 2022
Triggering
receptor
expressed
on
myeloid
cells
2
(TREM2)
is
a
single-pass
transmembrane
immune
that
mainly
microglia
in
the
brain
and
macrophages
periphery.
Recent
studies
have
identified
TREM2
as
risk
factor
for
Alzheimer's
disease
(AD).
Increasing
evidence
has
shown
can
affect
lipid
metabolism
both
central
nervous
system
(CNS)
In
CNS,
affects
of
cholesterol,
myelin,
phospholipids
promotes
transition
into
disease-associated
phenotype.
periphery,
influences
by
regulating
onset
progression
obesity
its
complications,
such
hypercholesterolemia,
atherosclerosis,
nonalcoholic
fatty
liver
disease.
All
these
altered
processes
could
influence
pathogenesis
AD
through
several
means,
including
affecting
inflammation,
insulin
resistance,
pathologies.
Herein,
we
will
discuss
potential
pathway
mediates
to
CNS
Moreover,
possibility
may
be
key
links
peripheral
under
conditions,
AD.
This
link
due
impacts
integrity
blood-brain
barrier,
introduce
pathways
which
barrier.
role
lipids
TREM2-associated
treatments
We
propose
some
therapies
targeting
prospect
limitations
therapies.
Molecular Neurodegeneration,
Journal Year:
2022,
Volume and Issue:
17(1)
Published: Dec. 23, 2022
Abstract
Microglia
are
central
players
in
brain
innate
immunity
and
have
been
the
subject
of
extensive
research
Alzheimer’s
disease
(AD).
In
this
review,
we
aim
to
summarize
genetic
functional
discoveries
that
advanced
our
understanding
microglia
reactivity
AD
pathology.
Given
heightened
risk
posed
by
rare
variants
microglial
triggering
receptor
expressed
on
myeloid
cells
2
(TREM2),
will
focus
studies
addressing
impact
responses
amyloid
plaques,
tauopathy
demyelination
pathologies
mouse
human.
Finally,
discuss
implications
recent
TREM2
biology
potential
therapeutic
strategies
for
AD.
Gastroenterology,
Journal Year:
2022,
Volume and Issue:
162(7), P. 1858 - 1875.e2
Published: March 3, 2022
Nonalcoholic
fatty
liver
disease
(NAFLD)
is
a
chronic
condition
affecting
one
quarter
of
the
global
population.
Although
primarily
linked
to
obesity
and
metabolic
syndrome,
undernutrition
altered
(dysbiotic)
gut
microbiome
influence
NAFLD
progression.
Both
prevalence
are
predicted
considerably
increase,
but
how
undernourished
contributes
hepatic
pathophysiology
remains
far
less
studied.
Here,
we
present
conditions
with
features,
including
kwashiorkor
micronutrient
deficiency.
We
then
review
microbiota-liver
axis,
highlighting
key
pathways
progression
within
both
overnutrition
undernutrition.
To
conclude,
identify
challenges
collaborative
possibilities
emerging
multiomic
research
addressing
pathology
treatment
NAFLD.
Gastroenterology,
Journal Year:
2023,
Volume and Issue:
165(1), P. 201 - 217
Published: April 5, 2023
Background
&
AimsNonalcoholic
steatohepatitis
(NASH)
is
characterized
by
steatosis,
lobular
inflammation,
hepatocyte
ballooning
degeneration,
and
fibrosis,
all
of
which
increase
the
risk
progression
to
end-stage
liver
disease.
Osteopontin
(OPN,
SPP1)
plays
an
important
role
in
macrophage
(MF)
biology,
but
whether
MF-derived
OPN
affects
NASH
unknown.MethodsWe
analyzed
publicly
available
transcriptomic
datasets
from
patients
with
NASH,
used
mice
conditional
overexpression
or
ablation
Spp1
myeloid
cells
MFs,
fed
them
a
high-fat,
fructose,
cholesterol
diet
mimicking
Western
diet,
induce
NASH.ResultsThis
study
demonstrated
that
MFs
high
expression
SPP1
are
enriched
nonalcoholic
fatty
disease
(NAFLD),
show
metabolic
not
pro-inflammatory
properties.
Conditional
knockin
(Spp1KI
Mye)
hepatic
macrophages
LvMF)
conferred
protection,
whereas
knockout
(Spp1ΔMye)
worsened
NASH.
The
protective
effect
was
mediated
induction
arginase-2
(ARG2),
enhanced
acid
oxidation
(FAO)
hepatocytes.
Induction
ARG2
stemmed
production
oncostatin-M
(OSM)
Spp1KI
Mye
mice.
OSM
activated
STAT3
signaling,
upregulated
ARG2.
In
addition
effects,
also
protected
through
sex-specific
extrahepatic
mechanisms.ConclusionMF-derived
protects
upregulating
OSM,
increases
signaling.
Further,
ARG2-mediated
FAO
reduces
steatosis.
Therefore,
enhancing
OPN–OSM–ARG2
crosstalk
between
hepatocytes
may
be
beneficial
for
Nonalcoholic
unknown.
We
This
mechanisms.
Molecular Aspects of Medicine,
Journal Year:
2023,
Volume and Issue:
95, P. 101231 - 101231
Published: Dec. 5, 2023
Liver
fibrosis,
as
an
excess
deposition
of
extracellular
matrix
(ECM)
components,
results
from
chronic
liver
injury
well
persistent
activation
inflammatory
response
and
fibrogenesis.
fibrosis
is
a
major
determinant
for
disease
(CLD)
progression
in
the
last
two
decades
our
understanding
on
molecular
cellular
mechanisms
underlying
fibrogenic
CLD
has
dramatically
improved,
boosting
pre-clinical
studies
clinical
trials
designed
to
find
novel
therapeutic
approaches.
From
these
several
critical
concepts
have
emerged,
starting
reveal
complexity
pro-fibrotic
microenvironment
which
involves
very
complex,
dynamic
interrelated
interactions
between
different
hepatic
extrahepatic
cell
populations.
This
review
will
offer
first
recapitulation
established
pathophysiological
basic
principles
by
intentionally
focus
attention
NAFLD/NASH,
metabolic-related
form
with
high
impact
general
population
emerging
leading
cause
worldwide.
NAFLD/NASH-related
pro-inflammatory
profibrogenic
be
analysed
information
cells,
mediators
signalling
pathways
taken
advantage
methodological
approaches
techniques
(single
genomics,
imaging
mass
cytometry,
vitro
two-
three-dimensional
models,
etc.).
We
next
overview
recent
advancement
diagnostic
prognostic
tools,
including
serum
biomarkers
polygenic
scores,
support
analysis
biopsies.
Finally,
this
provide
current
therapies
treatment
NAFLD/NASH
patients.