Current Opinion in Cell Biology,
Год журнала:
2024,
Номер
89, С. 102395 - 102395
Опубликована: Июль 5, 2024
The
exocytic
and
endocytic
intracellular
trafficking
pathways
in
innate
immune
cells
are
known
for
mediating
the
secretion
of
key
inflammatory
mediators
or
internalization
growth
factors,
nutrients,
antigens,
cell
debris,
pathogens
even
therapeutics,
respectively.
Inside
cells,
these
intertwined
as
an
elaborate
network
that
supports
regulation
functions.
Endosomal
membranes
host
dynamic
platforms
molecular
complexes
control
signaling
responses.
High
content
screens,
coupled
with
elegant
microscopy
across
scale
resolving
to
tracking
live
cellular
organelles,
have
been
employed
generate
studies
highlighted
here.
With
a
focus
on
deactivation
STING,
scaffolding
by
SLC15A4/TASL
macropinosome
shrinkage
via
chloride
channel
protein
TMEM206,
new
identifying
molecules,
interactions
mechanisms
throughout
endosomal
pathways.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Сен. 14, 2023
PHT1
is
a
histidine
/oligopeptide
transporter
with
an
essential
role
in
Toll-like
receptor
innate
immune
responses.
It
can
act
as
by
recruiting
the
adaptor
protein
TASL
which
leads
to
type
I
interferon
production
via
IRF5.
Persistent
stimulation
of
this
signalling
pathway
known
be
involved
pathogenesis
systemic
lupus
erythematosus
(SLE).
Understanding
how
recruits
at
molecular
level,
therefore
clinically
important
for
development
therapeutics
against
SLE
and
other
autoimmune
diseases.
Here
we
present
Cryo-EM
structure
stabilized
outward-open
conformation.
By
combining
biochemical
structural
modeling
techniques
propose
model
PHT1-TASL
complex,
first
16
N-terminal
residues
fold
into
helical
that
bind
central
cavity
inward-open
conformation
PHT1.
This
work
provides
critical
insights
basis
PHT1/TASL
mediated
production.
ABSTRACT
Haemophilus
ducreyi
causes
the
genital
ulcer
disease
chancroid
and
cutaneous
ulcers
in
children.
To
study
its
pathogenesis,
we
developed
a
human
challenge
model
which
infect
skin
on
upper
arm
of
volunteers
with
H.
to
pustular
stage
disease.
The
has
been
used
define
lesional
architecture,
describe
immune
infiltrate
into
infected
sites
using
flow
cytometry,
explore
molecular
basis
response
bulk
RNA-seq.
Here,
single
cell
RNA-seq
(scRNA-seq)
spatial
transcriptomics
simultaneously
characterize
multiple
types
within
determine
cellular
origin
differentially
expressed
transcripts
that
had
previously
identified
by
We
obtained
paired
biopsies
pustules
wounded
(mock
infected)
from
five
for
scRNA-seq.
13
major
types,
including
T-
NK-like
cells,
macrophages,
dendritic
as
well
other
typically
found
skin.
Immune
were
enriched
pustules,
some
subtypes
exclusive
pustules.
Sufficient
tissue
specimens
available
four
volunteers.
cells
highly
associated
antigen
presentation
types.
In
type
I
interferon
stimulation
was
high
areas
presentation—especially
macrophages
near
abscess—compared
wounds.
Together,
our
data
provide
high-resolution
view
infection
pathogen.
IMPORTANCE
A
due
an
extracellular
bacterial
pathogen
not
yet
defined.
identify
level
are
present
who
fail
spontaneously
clear
form
immune-activated
stromal
compared
sites.
Pustules
formed
despite
expression
pro-inflammatory
cytokines,
such
IL-1β
interferon.
Interferon
most
evident
proximal
abscess.
pustule
may
be
tempered
regulatory
T
express
indoleamine
2,3-dioxygenase,
leading
failure
system
.
International Reviews of Immunology,
Год журнала:
2025,
Номер
unknown, С. 1 - 15
Опубликована: Апрель 21, 2025
Systemic
lupus
erythematosus
(SLE)
is
a
prototypical
autoimmune
disease
characterized
by
excessive
production
of
type
I
interferons
(IFNs)
and
autoantibodies
with
limited
effective
clinical
treatments.
Solute
carrier
family
15
member
4
(SLC15A4),
proton-coupled
oligopeptide
transporter,
facilitates
the
transmembrane
transport
L-histidine
some
di-
tripeptides
from
lysosome
to
cytosol.
A
growing
body
evidence
has
elucidated
critical
role
SLC15A4
in
pathogenesis
progression
SLE.
Genome-wide
association
studies
have
identified
as
new
susceptibility
locus
Further
mechanistical
demonstrated
that
involves
IFNs
plasmacytoid
dendritic
cells
(pDCs)
its
necessity
B
for
autoantibody
models.
These
strongly
support
potential
promising
therapeutic
target
This
review
aims
summarize
recent
advances
understanding
SLE
development
SLC15A4-targeted
inhibitors
well
discuss
treatment.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Сен. 15, 2023
Amino
acid
transporters
are
generally
recognized
as
machinery
that
transport
amino
acids
from
the
extracellular
environment
into
cytoplasm.
Although
their
primary
function
is
uptake
of
to
supply
cell
with
nutrients
and
energy,
endolysosome-resident
(EL-aa)
possess
several
unique
functions
in
accordance
localization
intracellular
vesicular
membranes.
They
play
pivotal
roles
maintenance
metabolic
homeostasis
via
direct
involvement
sensing
pathway,
which
regulates
activity
mechanistic
target
rapamycin
complex
1
(mTORC1),
a
master
regulator
cellular
metabolism.
Additionally,
some
EL-aa
contribute
dynamic
endolysosomes,
including
regulation
endolysosomal
acidity,
by
carrying
out
endolysosomes.
In
addition,
act
scaffold
gather
signaling
molecules
multiple
enzymes
control
metabolism
on
membrane.
Among
transporters,
solute
carrier
family
15
member
4
(SLC15A4)
preferentially
expressed
immune
cells,
macrophages,
dendritic
B
plays
key
role
integration
inflammatory
signals.
this
review,
we
summarize
our
recent
findings
transporter
contributions
endolysosomes
cells
focusing
SLC15
family,
SLC15A4
SLC15A3,
discuss
uniqueness
universality.
We
also
potential
targeting
these
for
development
novel
therapeutic
strategies
diseases.
Because
highly
significantly
alter
them
would
provide
great
advantage
ensuring
wide
safety
margin.
International Immunology,
Год журнала:
2024,
Номер
37(1), С. 15 - 24
Опубликована: Июль 1, 2024
Chronic
inflammation
is
implicated
in
many
types
of
diseases,
including
cardiovascular,
neurodegenerative,
metabolic,
and
immune
disorders.
The
search
for
therapeutic
targets
to
control
chronic
often
involves
narrowing
down
the
various
molecules
associated
with
pathology
that
have
been
discovered
by
omics
analyses.
Herein,
a
different
approach
identify
against
proposed
one
such
target
discussed
as
an
example.
In
chronically
inflamed
tissues,
large
number
cells
receive
diverse
proinflammatory
signals,
intracellular
signals
are
intricately
integrated,
complicated
intercellular
interactions
orchestrated.
This
review
focuses
on
effectively
blocking
this
chaotic
inflammatory
signaling
network
via
endolysosomal
system,
which
acts
cellular
hub.
endolysosomes,
mediated
pathogen
sensors,
Toll-like
receptors,
from
nutrient
metabolic
pathways
integrally
regulated.
Disruption
endolysosome
results
strong
anti-inflammatory
effect
disrupting
pathways,
sensor-mediated
multiple
cells.
endolysosome-resident
amino
acid
transporter,
solute
carrier
family
15
member
4
(SLC15A4),
plays
important
role
regulation
endolysosome-mediated
promising
several
autoimmune
diseases.
mechanisms
SLC15A4
regulates
responses
may
provide
proof
concept
efficacy
strategies
targeting
cell
endolysosomes.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
222(3)
Опубликована: Дек. 10, 2024
Toll-like
receptors
(TLRs)
are
central
to
initiate
immune
responses
against
invading
pathogens.
To
ensure
host
defense
while
avoiding
aberrant
activation
leading
pathogenic
inflammation
and
autoimmune
diseases,
TLRs
tightly
controlled
by
multilevel
regulatory
mechanisms.
Through
a
loss-of-function
genetic
screen
in
reporter
cell
line
engineered
undergo
death
upon
TLR7-induced
IRF5
activation,
we
identified
here
CCDC134
as
an
essential
factor
for
TLR
responses.
deficiency
impaired
endolysosomal
TLR-induced
NF-κB,
MAPK,
well
downstream
production
of
proinflammatory
cytokines
type
I
interferons.
We
further
demonstrated
that
is
endoplasmic
reticulum
(ER)-resident
interactor
Gp96
(HSP90B1/Grp94),
ER
chaperone
folding
trafficking
plasma
membrane
TLRs.
stability
its
loss
led
hyperglycosylation
ER-associated
protein
degradation
(ERAD)-mediated
clearance.
Accordingly,
the
folding,
maturation,
TLRs,
resulting
blunted
inflammatory
stimulation.
Altogether,
this
study
reveals
regulator
Gp96,
thereby
controlling
biogenesis
In
bacteria,
the
cell
envelope
is
key
element
surrounding
and
protecting
bacterial
content
from
mechanical
or
osmotic
damages.
It
allows
selective
interchanges
of
solutes,
ions,
cellular
debris,
drugs
between
compartments
external
environment,
thanks
to
presence
transmembrane
proteins
called
transporters.
The
major
component
peptidoglycan,
consisting
long
linear
glycan
strands
cross-linked
by
short
peptide
stems.
During
growth
under
stress
conditions,
peptidoglycan
fragments,
muropeptides,
are
released
bacteria
recognized
host
Pattern
Recognition
Receptor,
promoting
activation
their
innate
defense
mechanisms.
review
sums
up
salient
aspects
microbiota-host
interaction
with
a
focus
on
NOD-dependent
immune
response
accountability
muropeptide
transporters
in
crosstalk
antibiotic
resistance.
Furthermore,
it
retraces
discoveries
applications
microorganisms-derived
components
such
as
vaccines
vaccine
adjuvants.