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Apoptotic Cells Ameliorate Chronic Intestinal Inflammation by Enhancing Regulatory B-cell Function.
[severe combined immunodeficiency]
:
Apoptosis
is
a
programmed
physiological
death
of
unwanted
cells
,
and
handling
of
apoptotic
cells
(
ACs
)
is
thought
to
have
profound
effects
on
immune-mediated
disorders
.
However
,
there
is
scant
information
regarding
the
role
of
ACs
in
intestinal
inflammation
,
in
which
immune
homeostasis
is
a
major
concern
.
To
investigate
this
,
we
injected
ACs
into
a
severe
combined
immunodeficiency
adoptive
transfer
model
of
chronic
colitis
in
the
presence
and
absence
of
cotransferred
whole
B
or
regulatory
B
cell
(
Breg
)
-
depleted
B
cells
.
We
also
injected
syngeneic
ACs
into
AKR
/
N
mice
as
a
control
and
into
milk
fat
globule-
epidermal
growth
factor
8
knockout
mice
deficient
of
phagocytic
function
.
Chronic
colitis
severity
was
significantly
reduced
in
the
AC
as
opposed
to
the
phosphate-buffered
saline
group
with
cotransferred
whole
B
cells
.
The
AC-mediated
effect
was
lost
in
the
absence
of
B
cells
or
presence
of
Breg-depleted
B
cells
.
In
addition
,
ACs
induced
splenic
B
cells
to
secrete
significantly
increased
levels
of
interleukin
10
in
AKR
/
N
mice
but
not
milk
fat
globule-
epidermal
growth
factor
8
knockout
mice
.
Apoptotic
leukocytes
were
induced
by
reactive
oxygen
species
during
granulocyte
/
monocyte
apheresis
therapy
in
rabbits
and
H
2
O
2
-
induced
apoptotic
neutrophils
ameliorated
mice
colitis
.
Our
results
indicate
that
ACs
are
protective
only
in
the
presence
of
B
cells
and
phagocytosis
of
ACs
induced
interleukin
10
producing
Bregs
.
Thus
,
the
ameliorative
effect
seen
in
this
study
might
have
been
exerted
by
AC-induced
Bregs
through
increased
production
of
the
immunosuppressive
cytokine
interleukin
10
,
whereas
an
AC-mediated
effect
may
contribute
to
the
anti-
inflammatory
effect
of
granulocyte
/
monocyte
apheresis
as
a
novel
therapeutic
mechanism
for
inflammatory
bowel
disease
.
Diseases
Validation
Diseases presenting
"inflammatory bowel disease"
symptom
acute rheumatic fever
benign recurrent intrahepatic cholestasis
cholangiocarcinoma
familial mediterranean fever
hirschsprung disease
legionellosis
malignant atrophic papulosis
primary effusion lymphoma
severe combined immunodeficiency
typhoid
This symptom has already been validated