Science Immunology,
Journal Year:
2023,
Volume and Issue:
8(83)
Published: May 26, 2023
The
ability
of
most
patients
with
selective
immunoglobulin
A
(IgA)
deficiency
(SIgAD)
to
remain
apparently
healthy
has
been
a
persistent
clinical
conundrum.
Compensatory
mechanisms,
including
IgM,
have
proposed,
yet
it
remains
unclear
how
secretory
IgA
and
IgM
work
together
in
the
mucosal
system
and,
on
larger
scale,
whether
systemic
anti-commensal
responses
are
redundant
or
unique
features.
To
address
this
gap
knowledge,
we
developed
an
integrated
host-commensal
approach
combining
microbial
flow
cytometry
metagenomic
sequencing
(mFLOW-Seq)
comprehensively
define
which
microbes
induce
antibodies.
We
coupled
high-dimensional
immune
profiling
study
cohort
pediatric
SIgAD
household
control
siblings.
found
that
antibody
networks
cooperate
maintain
homeostasis
by
targeting
common
subset
commensal
microbes.
In
IgA-deficiency,
find
increased
translocation
specific
bacterial
taxa
associated
elevated
levels
IgG
fecal
microbiota.
Associated
features
dysregulation
IgA-deficient
mice
humans
included
inflammatory
cytokines,
enhanced
follicular
CD4
T
helper
cell
frequency
activation,
altered
CD8
activation
state.
Although
is
clinically
defined
absence
serum
IgA,
symptomatology
were
concentrated
participants
who
also
deficient.
These
findings
reveal
leads
aberrant
exposures
microbes,
increase
likelihood
humoral
cellular
symptomatic
disease
deficiency.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(44)
Published: Oct. 23, 2023
The
immune
system
is
a
complex
network
of
cells
with
critical
functions
in
health
and
disease.
However,
comprehensive
census
the
comprising
lacking.
Here,
we
estimated
abundance
primary
cell
types
throughout
all
tissues
human
body.
We
conducted
literature
survey
integrated
data
from
multiplexed
imaging
methylome-based
deconvolution.
also
considered
cellular
mass
to
determine
distribution
terms
both
number
total
mass.
Our
results
indicate
that
reference
73
kg
man
consists
1.8
×
10
12
(95%
CI
1.5–2.3
),
weighing
1.2
0.8–1.9).
Lymphocytes
constitute
40%
15%
are
mainly
located
lymph
nodes
spleen.
Neutrophils
account
for
similar
proportions
cells,
most
neutrophils
residing
bone
marrow.
Macrophages,
present
tissues,
10%
but
contribute
nearly
50%
due
their
large
size.
quantification
within
body
presented
here
can
serve
understand
function
better
facilitate
quantitative
modeling
this
vital
system.
EBioMedicine,
Journal Year:
2022,
Volume and Issue:
76, P. 103798 - 103798
Published: Jan. 27, 2022
Multiple
sclerosis
(MS)
has
a
complex
genetic,
immune
and
metabolic
pathophysiology.
Recent
studies
implicated
the
gut
microbiome
in
MS
pathogenesis.
However,
interactions
between
host
system,
metabolism
diet
have
not
been
studied
over
time
this
disorder.We
performed
six-month
longitudinal
multi-omics
study
of
49
participants
(24
untreated
relapse
remitting
patients
25
age,
sex,
race
matched
healthy
control
individuals.
Gut
composition
function
were
characterized
using
16S
metagenomic
shotgun
sequencing.
Flow
cytometry
was
used
to
characterize
blood
cell
populations
cytokine
profiles.
Circulating
metabolites
profiled
by
untargeted
UPLC-MS.
A
four-day
food
diary
recorded
capture
habitual
dietary
pattern
participants.Together
with
changes
cells,
analysis
identified
number
microbiota
decreased
compared
controls,
positively
or
negatively
correlated
degree
disability
patients.
demonstrated
perturbations
their
metabolome,
such
as
linoleate
pathway,
fatty
acid
biosynthesis,
chalcone,
dihydrochalcone,
4-nitrocatechol
methionine.
Global
correlations
disrupted
immune-microbiome
relationship
positive
metabolome-microbiome
correlation
MS.
Specific
feature
association
potential
network
linking
meat
servings
microbe
B.
thetaiotaomicron,
increased
Th17
greater
abundance
meat-associated
metabolites.
The
metabolome
profiles
remained
stable
six
months
individuals.Our
multi-system
alterations
microbiota,
at
global
individual
level.
Multi-OMICS
data
integration
deciphered
important
biological
that
links
intakes
metabolite,
polysaccharides
digesting
bacteria,
circulating
proinflammatory
marker.This
work
supported
Washington
University
St.
Louis
Institute
Clinical
Translational
Sciences,
funded,
part,
Grant
Number
#
UL1
TR000448
from
National
Institutes
Health,
Center
for
Advancing
Sciences
Award
(Zhou
Y,
Piccio,
L,
Lovett-Racke
Tarr
PI);
R01
NS10263304
Piccio
L);
Leon
Harriet
Felman
Fund
Human
Research
(Piccio
L
Cross
AH).
Cantoni
C.
Society
Career
Transition
Fellowship
(TA-180531003)
donations
Whitelaw
Terry,
Jr.
/
Valerie
Terry
Fund.
Ghezzi
L.
Italian
Sclerosis
research
fellowship
(FISM
2018/B/1)
Post-Doctoral
(FG-190734474).
Anne
Manny
&
Rosalyn
Rosenthal-Dr.
John
Trotter
Chair
Neuroimmunology
Barnes-Jewish
Hospital
Foundation.
content
is
solely
responsibility
authors
does
necessarily
represent
official
views
Health.
Trends in Cognitive Sciences,
Journal Year:
2023,
Volume and Issue:
27(3), P. 246 - 257
Published: Feb. 2, 2023
Neuroimaging
research
has
been
at
the
forefront
of
concerns
regarding
failure
experimental
findings
to
replicate.
In
study
brain-behavior
relationships,
past
failures
find
replicable
and
robust
effects
have
attributed
methodological
shortcomings.
Methodological
rigor
is
important,
but
there
are
other
overlooked
possibilities:
most
published
studies
share
three
foundational
assumptions,
often
implicitly,
that
may
be
faulty.
this
paper,
we
consider
empirical
evidence
from
human
brain
imaging
non-human
animals
calls
each
assumption
into
question.
We
then
opportunities
for
a
science
relationships
await
if
scientists
ground
their
efforts
in
revised
assumptions
supported
by
current
evidence.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(5), P. 4546 - 4546
Published: Feb. 25, 2023
Aging
can
be
seen
as
a
physiological
progression
of
biomolecular
damage
and
the
accumulation
defective
cellular
components,
which
trigger
amplify
process,
toward
whole-body
function
weakening.
Senescence
initiates
at
level
consists
in
an
inability
to
maintain
homeostasis,
characterized
by
overexpression/aberrant
expression
inflammatory/immune/stress
responses.
is
associated
with
significant
modifications
immune
system
cells,
decline
immunosurveillance,
which,
turn,
leads
chronic
elevation
inflammation/oxidative
stress,
increasing
risk
(co)morbidities.
Albeit
aging
natural
unavoidable
it
regulated
some
factors,
like
lifestyle
diet.
Nutrition,
indeed,
tackles
mechanisms
underlying
molecular/cellular
aging.
Many
micronutrients,
i.e.,
vitamins
elements,
impact
cell
function.
This
review
focuses
on
role
exerted
vitamin
D
geroprotection,
based
its
ability
shape
cellular/intracellular
processes
drive
response
protection
against
infections
age-related
diseases.
To
this
aim,
main
paths
immunosenescence
inflammaging
are
identified
biotargets
D.
Topics
such
heart
skeletal
muscle
function/dysfunction,
depending
status,
addressed,
comments
hypovitaminosis
correction
food
supplementation.
research
has
progressed,
still
limitations
exist
translating
knowledge
into
clinical
practice,
making
necessary
focus
attention
aging,
especially
considering
growing
number
older
individuals.
Science Immunology,
Journal Year:
2023,
Volume and Issue:
8(83)
Published: May 26, 2023
The
ability
of
most
patients
with
selective
immunoglobulin
A
(IgA)
deficiency
(SIgAD)
to
remain
apparently
healthy
has
been
a
persistent
clinical
conundrum.
Compensatory
mechanisms,
including
IgM,
have
proposed,
yet
it
remains
unclear
how
secretory
IgA
and
IgM
work
together
in
the
mucosal
system
and,
on
larger
scale,
whether
systemic
anti-commensal
responses
are
redundant
or
unique
features.
To
address
this
gap
knowledge,
we
developed
an
integrated
host-commensal
approach
combining
microbial
flow
cytometry
metagenomic
sequencing
(mFLOW-Seq)
comprehensively
define
which
microbes
induce
antibodies.
We
coupled
high-dimensional
immune
profiling
study
cohort
pediatric
SIgAD
household
control
siblings.
found
that
antibody
networks
cooperate
maintain
homeostasis
by
targeting
common
subset
commensal
microbes.
In
IgA-deficiency,
find
increased
translocation
specific
bacterial
taxa
associated
elevated
levels
IgG
fecal
microbiota.
Associated
features
dysregulation
IgA-deficient
mice
humans
included
inflammatory
cytokines,
enhanced
follicular
CD4
T
helper
cell
frequency
activation,
altered
CD8
activation
state.
Although
is
clinically
defined
absence
serum
IgA,
symptomatology
were
concentrated
participants
who
also
deficient.
These
findings
reveal
leads
aberrant
exposures
microbes,
increase
likelihood
humoral
cellular
symptomatic
disease
deficiency.