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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
"chronic colitis"
symptom
kindler syndrome
severe combined immunodeficiency
This symptom has already been validated