RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis
Cell Death and Differentiation,
Год журнала:
2024,
Номер
31(6), С. 820 - 832
Опубликована: Май 11, 2024
Abstract
The
T
cell
population
size
is
stringently
controlled
before,
during,
and
after
immune
responses,
as
improper
death
regulation
can
result
in
autoimmunity
immunodeficiency.
RIPK1
an
important
regulator
of
peripheral
survival
homeostasis.
However,
whether
different
subsets
show
a
differential
requirement
for
which
programmed
pathway
they
engage
vivo
remains
unclear.
In
this
study,
we
demonstrate
that
conditional
ablation
Ripk1
conventional
cells
(
ΔCD4
)
causes
lymphopenia,
witnessed
by
profound
loss
naive
CD4
+
,
CD8
FoxP3
regulatory
cells.
Interestingly,
mice
appear
to
undergo
selective
pressure
retain
expression
following
activation.
Mixed
bone
marrow
chimeras
revealed
competitive
disadvantage
naive,
effector,
memory
lacking
RIPK1.
Additionally,
tamoxifen-induced
deletion
CD4-expressing
adult
life
confirmed
the
importance
post-thymic
K45A
showed
no
change
subsets,
demonstrating
lymphopenia
was
due
scaffold
function
rather
than
its
kinase
activity.
Enhanced
numbers
expressed
proliferation
marker
Ki-67
despite
single-cell
RNA
sequencing
cell-specific
transcriptomic
alterations
were
reverted
additional
caspase-8
deficiency.
Furthermore,
Casp8
Tnfr1
−/−
double-knockout
rescued
revealing
RIPK1-deficient
specifically
die
from
TNF-
caspase-8-mediated
apoptosis
vivo.
Altogether,
our
findings
emphasize
essential
role
maintaining
compartment
preventing
TNFR1-induced
apoptosis.
Язык: Английский
Everything everywhere all at once: Unraveling the waves of aging
Immunity,
Год журнала:
2025,
Номер
58(2), С. 276 - 278
Опубликована: Фев. 1, 2025
Язык: Английский
Targeting T-cell Aging to Remodel the Aging Immune System and Revitalize Geriatric Immunotherapy
Aging and Disease,
Год журнала:
2025,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2025
The
aging
immune
system
presents
profound
challenges,
notably
through
the
decline
of
T
cell
function,
which
is
critical
for
effective
responses.
As
age-related
changes
lead
to
diminished
diversity
and
heighten
immunosuppressive
environments,
older
individuals
face
increased
susceptibility
infections,
autoimmune
diseases,
reduced
efficacy
immunotherapies.
This
review
investigates
intricate
mechanisms
by
drives
immunosenescence,
including
suppression,
evasion,
antigen
reactivity,
overexpression
checkpoint
molecules.
By
delving
into
innovative
therapeutic
strategies
aimed
at
rejuvenating
populations
modifying
immunological
landscape,
we
highlight
potential
enhancing
resilience
in
elderly.
Ultimately,
our
goal
outline
actionable
pathways
restoring
thereby
improving
health
outcomes
facing
decline.
Язык: Английский
RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy
EMBO Reports,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 30, 2025
RIPK1
is
a
crucial
regulator
of
cell
survival,
inflammation
and
death.
Human
deficiency
leads
to
early-onset
intestinal
peripheral
T
imbalance,
though
its
role
in
αβT
cell-mediated
homeostasis
remains
unclear.
In
this
study,
we
demonstrate
that
mice
with
ablation
conventional
cells
(Ripk1ΔCD4)
developed
severe
small
pathology
characterized
by
elongation,
crypt
hyperplasia,
duodenum-specific
villus
atrophy.
Using
mixed
bone
marrow
chimeras
reveals
survival
disadvantage
compared
γδT
the
intestine.
Broad-spectrum
antibiotic
treatment
ameliorates
hyperplasia
prevents
atrophy
persists.
Conversely,
crossing
Ripk1ΔCD4
TNF
receptor
1
Tnfr1-/-
knockout
rescues
but
not
elongation.
Finally,
combined
Ripk1∆CD4
Casp8∆CD4
fully
pathology,
revealing
apoptosis
drives
enteropathy.
These
findings
RIPK1-mediated
essential
for
proximal
homeostasis.
mice,
imbalanced
compartment
microbiome-mediated
elongation
TNF-driven
Язык: Английский
Excessive apoptosis of Rip1‐deficient T cells leads to premature aging
EMBO Reports,
Год журнала:
2023,
Номер
24(12)
Опубликована: Ноя. 15, 2023
Язык: Английский
Not to be and how not to be: the questions of Tregs controlled by RIPK1
Cellular and Molecular Immunology,
Год журнала:
2024,
Номер
21(2), С. 205 - 206
Опубликована: Янв. 15, 2024
Язык: Английский
The network structural entropy for single-cell RNA sequencing data during skin aging
Briefings in Bioinformatics,
Год журнала:
2024,
Номер
26(1)
Опубликована: Ноя. 22, 2024
Abstract
Aging
is
a
complex
and
heterogeneous
biological
process
at
cellular,
tissue,
individual
levels.
Despite
extensive
effort
in
scientific
research,
comprehensive
understanding
of
aging
mechanisms
remains
lacking.
This
study
analyzed
aging-related
gene
networks,
using
single-cell
RNA
sequencing
data
from
>15
000
cells.
We
constructed
correlation
network,
integrating
expressions
into
the
weights
network
edges,
ranked
importance
random
walk
model
to
generate
matrix.
unsupervised
method
improved
clustering
performance
cell
types.
To
further
quantify
complexity
networks
during
aging,
we
introduced
structural
entropy.
The
findings
our
reveal
that
overall
entropy
increases
aged
cells
compared
young
However,
changes
varied
greatly
within
different
subtypes.
Specifically,
among
various
types
may
increase,
remain
unchanged,
or
decrease.
wide
range
be
closely
related
their
functions,
highlighting
cellular
heterogeneity
potential
key
reconfigurations.
Analyzing
provides
insights
molecular
behind
aging.
offers
new
evidence
theoretical
support
for
functions
Язык: Английский