Genetic diversity leads to differential inflammatory responses to cigarette smoke in mice
Physiological Reports,
Год журнала:
2025,
Номер
13(2)
Опубликована: Янв. 1, 2025
Abstract
The
use
of
genetically
diverse
mouse
models
offers
a
more
accurate
reflection
human
genetic
variability,
improving
the
translatability
findings
to
heterogeneous
populations.
This
approach
is
particularly
valuable
in
understanding
immune
responses
disease
by
environmental
exposures.
study
investigates
inflammatory
acute
exposures
mainstream
cigarette
smoke
(CS)
and
tobacco
(ETS)
two
strains,
CC002/UncJ
(UNC)
&
Diversity
Outbred
(J:DO).
UM‐HET3
(HET3)
strain,
typically
used
aging
intervention
studies,
has
also
been
evaluate
this
model
for
age‐associated
pathologies.
involves
comprehensive
approach,
including
BALF
cytokine
analysis,
evaluation
lung
tissue
architecture,
assessment
macrophages
its
associated
proteins
(MMP9
MMP12)
abundance.
Several
cytokines/chemokines
were
found
be
upregulated
across
three
strains.
Notably,
UNC
strain
exclusively
showed
upregulation
TNF‐α,
IL‐17A,
IL‐13,
whereas
J:DO
an
KC.
number
alveolar
lungs
mice
was
very
low
at
baseline
compared
other
strains
studied
study,
which
indicative
some
inherent
shift
pulmonary
profiles
these
inbred
mice.
In
contrast,
characterized
outbreeding,
much
robust
macrophage
response
comparable
C57BL/6J.
provide
insight
into
how
diversity
affects
CS/ETS
exposure,
with
implications
stressors
studying
pathophysiology.
Язык: Английский
Noncanonical T cell responses are associated with protection from tuberculosis in mice and humans
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(7)
Опубликована: Апрель 7, 2025
While
control
of
Mycobacterium
tuberculosis
(Mtb)
infection
is
generally
understood
to
require
Th1
cells
and
IFNγ,
produces
a
spectrum
immunological
pathological
phenotypes
in
diverse
human
populations.
By
characterizing
Mtb
mouse
strains
that
model
the
genetic
heterogeneity
an
outbred
population,
we
identified
comparably
standard
IFNγ-dependent
but
with
substantially
lower
lung
IFNγ
levels.
We
report
these
mice
have
significantly
altered
CD4
T
cell
profile
specifically
lacks
terminal
effector
subset
this
phenotype
detectable
before
infection.
These
still
bacterial
burden
are
less
dependent
on
signaling.
Instead,
noncanonical
immune
features
such
as
Th17-like
γδT
correlate
low
burden.
find
same
Th17
transcriptional
programs
associated
resistance
humans,
implicating
specific
non-Th1
responses
common
feature
across
species.
Язык: Английский
Probing the basis of disease heterogeneity in multiple sclerosis using genetically diverse mice
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 4, 2024
Multiple
sclerosis
(MS)
is
a
complex
disease
with
significant
heterogeneity
in
course
and
progression.
Genetic
studies
have
identified
numerous
loci
associated
MS
risk,
but
the
genetic
basis
of
progression
remains
elusive.
To
address
this,
we
leveraged
Collaborative
Cross
(CC),
genetically
diverse
mouse
strain
panel,
experimental
autoimmune
encephalomyelitis
(EAE).
The
thirty-two
CC
strains
studied
captured
wide
spectrum
EAE
severity,
trajectory,
presentation,
including
severe-progressive,
monophasic,
relapsing
remitting,
axial
rotary
(AR)-EAE,
accompanied
by
distinct
immunopathology.
Sex
differences
severity
were
observed
six
strains.
Quantitative
trait
locus
analysis
revealed
linkage
patterns
for
different
phenotypes,
incidence
AR-EAE.
Machine
learning-based
approaches
prioritized
candidate
genes
underlying
(
Язык: Английский