Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Март 3, 2022
Innate
immunity
is
the
first
defense
system
against
invading
pathogens.
Toll-like
receptors
(TLRs)
are
well-defined
pattern
recognition
responsible
for
pathogen
and
induction
of
innate
immune
responses.
Since
their
discovery,
TLRs
have
revolutionized
field
immunology
by
filling
gap
between
initial
pathogens
cells
activation
adaptive
response.
critically
link
to
regulating
antigen-presenting
key
cytokines.
Furthermore,
recent
studies
also
shown
that
TLR
signaling
can
directly
regulate
T
cell
activation,
growth,
differentiation,
development,
function
under
diverse
physiological
conditions.
This
review
provides
an
overview
pathways
regulators
discusses
how
signaling,
indirectly,
regulates
cell-mediated
immunity.
In
addition,
we
discuss
important
in
host’s
infectious
diseases,
autoimmune
cancer.
Systemic
lupus
erythematosus
(SLE)
is
a
complex
autoimmune
disease
with
multisystem
involvement.
It
multifactorial
and
involves
epigenetic,
genetic,
ecological,
environmental
factors.
Primarily
it
leads
to
activation
of
both
innate
adaptive
immunity,
which
consequently
autoreactive
B
cell
by
T
cells
immune
complexes
deposition
in
tissues
leading
an
cascade
that
may
be
limited
the
single
organ
or
can
cause
widespread
systemic
SLE
heterogeneous
presentation,
broad
spectrum
clinical
manifestations
ranging
from
clinically
mild
self-resolving
symptoms
severe
life-threatening
Clinical
serological
heterogeneity
are
critical
features
SLE,
posing
significant
challenge
its
diagnosis.
Antinuclear
antibodies
(ANA)
telltale
marker
more
than
95%
patients.
The
improved
set
European
Alliance
Associations
for
Rheumatology
(EULAR)
classification
enabled
accurate
diagnosis
SLE.
treatment
focuses
on
remission,
preventing
damage,
improving
overall
quality
life.
Toll-like
receptors
(TLRs)
are
inflammatory
triggers
and
belong
to
a
family
of
pattern
recognition
(PRRs)
that
central
the
regulation
host
protective
adaptive
immune
responses.
Activation
TLRs
in
innate
myeloid
cells
directs
lymphocytes
produce
most
appropriate
effector
responses
eliminate
infection
maintain
homeostasis
body's
internal
environment.
Inappropriate
TLR
stimulation
can
lead
development
general
autoimmune
diseases
as
well
chronic
acute
inflammation,
even
cancer.
Therefore,
expected
be
targets
for
therapeutic
treatment
inflammation-related
diseases,
microbial
infections,
human
cancers.
This
review
summarizes
recent
discoveries
molecular
structural
biology
TLRs.
The
role
different
signaling
pathways
such
diabetes,
cardiovascular
respiratory
digestive
cancers
(oral,
gastric,
breast,
colorectal)
is
highlighted
new
drugs
related
clinical
treatments
trials,
providing
an
overview
potential
prospects
TLR-related
diseases.
Annals of the Rheumatic Diseases,
Год журнала:
2024,
Номер
unknown, С. ard - 225727
Опубликована: Май 22, 2024
B
cells
have
a
pivotal
function
in
the
pathogenesis
of
autoimmune
diseases,
such
as
rheumatoid
arthritis,
multiple
sclerosis
and
systemic
lupus
erythematosus.
In
disease,
orchestrate
antigen
presentation,
cytokine
production
autoantibody
production,
latter
via
their
differentiation
into
antibody-secreting
plasmablasts
plasma
cells.
This
article
addresses
current
therapeutic
strategies
to
deplete
order
ameliorate
or
potentially
even
cure
disease.
It
main
target
antigens
B-cell
lineage
that
are
used
for
approaches.
Furthermore,
it
summarises
evidence
successful
treatment
disease
with
monoclonal
antibodies
targeting
limitations
challenges
these
Finally,
concept
deep
depletion
immunological
reset
by
chimeric
receptor
T
is
discussed,
well
lessons
from
this
approach
better
understanding
role
Applying
advanced
molecular
profiling
together
with
highly
specific
targeted
therapies
offers
the
possibility
to
better
dissect
mechanisms
underlying
immune-mediated
inflammatory
diseases
such
as
systemic
lupus
erythematosus
(SLE)
in
humans.
Here
we
apply
a
combination
of
single-cell
RNA-Seq
and
T/B
cell
repertoire
analysis
perform
an
in-depth
characterization
changes
immune-signature
upon
CD19
CAR
T
cell-mediated
depletion
B
cells
patients
SLE.
The
resulting
data
sets
not
only
confirm
selective
reset
response
but
simultaneously
reveal
consequent
transcriptional
signature
monocyte
subsets
that
respond
profound
reduction
type
I
IFN
signaling.
Our
current
data,
thus,
provide
evidence
for
causal
relationship
between
increased
observed
SLE
additionally
demonstrate
usefulness
combining
analytic
approaches
decipher
Science Translational Medicine,
Год журнала:
2025,
Номер
17(784)
Опубликована: Фев. 5, 2025
Chronic
autoimmune
diseases
often
lead
to
long-term
sequelae
and
require
lifelong
immunosuppression
because
of
an
incomplete
understanding
the
triggers
drivers
in
genetically
predisposed
patients.
Gut
bacteria
that
escape
gut
barrier,
known
as
translocating
pathobionts,
have
been
implicated
instigators
perpetuators
extraintestinal
mice.
The
microbial
contributions
autoimmunity
humans
remain
largely
unclear,
including
whether
specific
pathological
human
adaptive
immune
responses
are
triggered
by
such
pathobionts.
Here,
we
show
pathobiont
Enterococcus
gallinarum
can
induce
both
mouse
interferon-γ
+
T
helper
17
(T
H
17)
differentiation
immunoglobulin
G3
(IgG3)
subclass
switch
anti–
E.
RNA
antibodies,
which
correlated
with
anti-human
autoantibody
patients
systemic
lupus
erythematosus
(SLE)
hepatitis,
two
diseases.
RNA,
but
not
Toll-like
receptor
8
(TLR8),
TLR8-mediated
monocyte
activation
promoted
induction
.
Translocation
increased
anti-RNA
titers
renal
pathophysiology
murine
gnotobiotic
models
disease
activity
SLE.
These
studies
elucidate
cellular
mechanisms
how
a
induces
cell–
B
cell–dependent
provide
framework
for
developing
host-
microbiota-derived
biomarkers
targeted
therapies
Immunological Reviews,
Год журнала:
2022,
Номер
307(1), С. 79 - 100
Опубликована: Янв. 31, 2022
Abstract
Age‐associated
B
cells
(ABCs)
have
emerged
as
critical
components
of
immune
responses.
Their
inappropriate
expansion
and
differentiation
increasingly
been
linked
to
the
pathogenesis
autoimmune
disorders,
aging‐associated
diseases,
infections.
ABCs
exhibit
a
distinctive
phenotype
and,
in
addition
classical
cell
markers,
often
express
transcription
factor
T‐bet
myeloid
markers
like
CD11c;
hence,
these
are
also
commonly
known
CD11c
+
cells.
Formation
is
promoted
by
combinations
innate
adaptive
signals.
In
producing
antibodies,
display
antigen‐presenting
proinflammatory
capabilities.
It
becoming
appreciated
that
ABC
compartment
exhibits
high
degree
heterogeneity,
plasticity,
sex‐specific
regulation
can
differentiate
into
effector
progeny
via
several
routes
particularly
settings.
this
review,
we
will
discuss
initial
insights
obtained
on
molecular
machinery
controls
highlight
some
unique
aspects
control
system
may
enable
fulfill
their
role
Given
expanding
array
disorders
pathophysiological
settings
which
being
implicated,
deeper
understanding
could
important
broad
therapeutic
implications
for
successful,
albeit
daunting,
task
targeting
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Март 18, 2022
Systemic
lupus
erythematosus
(SLE)
is
a
heterogeneous
disease
characterized
by
the
production
of
abnormal
autoantibodies
and
immune
complexes
that
can
affect
organ
systems,
particularly
kidneys
cardiovascular
system.
Emerging
evidence
suggests
dysregulated
lipid
metabolism,
especially
in
key
effector
cells,
such
as
T
B
innate
exerts
complex
effects
on
pathogenesis
progression
SLE.
Beyond
their
important
roles
membrane
components
energy
storage,
different
lipids
also
modulate
cellular
processes,
proliferation,
differentiation,
survival.
In
this
review,
we
summarize
altered
metabolism
associated
mechanisms
involved
Furthermore,
discuss
recent
progress
role
potential
therapeutic
target
Cellular and Molecular Immunology,
Год журнала:
2022,
Номер
19(11), С. 1215 - 1234
Опубликована: Окт. 12, 2022
Abstract
B
cells
play
a
pivotal
role
in
the
pathogenesis
of
autoimmune
diseases.
Although
previous
studies
have
shown
many
genetic
polymorphisms
associated
with
B-cell
activation
patients
various
disorders,
progress
epigenetic
research
has
revealed
new
mechanisms
leading
to
hyperactivation.
Epigenetic
mechanisms,
including
those
involving
histone
modifications,
DNA
methylation,
and
noncoding
RNAs,
regulate
responses,
their
dysregulation
can
contribute
Patients
diseases
show
alterations
that
lead
initiation
perpetuation
inflammation.
Moreover,
clinical
animal
model
promising
potential
therapies
for
patients.
In
this
review,
we
present
an
up-to-date
overview
focus
on
roles
regulating
functional
subsets.
Furthermore,
discuss
highlight
its
contribution
development
Based
preclinical
evidence,
novel
biomarkers
disorders.
The Journal of Experimental Medicine,
Год журнала:
2022,
Номер
219(6)
Опубликована: Май 5, 2022
Sexual
dimorphism
in
the
composition
and
function
of
human
immune
system
has
important
clinical
implications,
as
males
females
differ
their
susceptibility
to
infectious
diseases,
cancers,
especially
systemic
autoimmune
rheumatic
diseases.
Both
sex
hormones
X
chromosome,
which
bears
a
number
immune-related
genes,
play
critical
roles
establishing
molecular
basis
for
observed
differences
dysfunction.
Here,
we
review
our
current
understanding
health
disease,
with
specific
focus
on
contribution
chromosome
striking
female
bias
three
