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Autophagy, inflammation and innate immunity in inflammatory myopathies.
[inclusion body myositis]
Autophagy
has
a
large
range
of
physiological
functions
and
its
dysregulation
contributes
to
several
human
disorders
,
including
autoinflammatory
/
autoimmune
diseases
such
as
inflammatory
myopathies
(
IIMs
)
.
In
order
to
better
understand
the
pathogenetic
mechanisms
of
these
muscular
disorders
,
we
sought
to
define
the
role
of
autophagic
processes
and
their
relation
with
the
innate
immune
system
in
the
three
main
subtypes
of
IIM
,
specifically
sporadic
inclusion
body
myositis
(
sIBM
)
,
polymyositis
(
PM
)
,
dermatomyositis
(
DM
)
and
juvenile
dermatomyositis
(
JDM
)
.
We
found
that
although
the
mRNA
transcript
levels
of
the
autophagy-related
genes
BECN
1
,
ATG
5
and
FBXO
32
were
similar
in
IIM
and
controls
,
autophagy
activation
in
all
IIM
subgroups
was
suggested
by
immunoblotting
results
and
confirmed
by
immunofluorescence
.
TLR
4
and
TLR
3
,
two
potent
inducers
of
autophagy
,
were
highly
increased
in
IIM
,
with
TLR
4
transcripts
significantly
more
expressed
in
PM
and
DM
than
in
JDM
,
sIBM
and
controls
,
and
TLR
3
transcripts
highly
up-regulated
in
all
IIM
subgroups
compared
to
controls
.
Co
-localization
between
autophagic
marker
,
LC
3
,
and
TLR
4
and
TLR
3
was
observed
not
only
in
sIBM
but
also
in
PM
,
DM
and
JDM
muscle
tissues
.
Furthermore
,
a
highly
association
with
the
autophagic
processes
was
observed
in
all
IIM
subgroups
also
for
some
TLR
4
ligands
,
endogenous
and
bacterial
HSP
60
,
other
than
the
high
-mobility
group
box
1
(
HMGB
1
)
.
These
findings
indicate
that
autophagic
processes
are
active
not
only
in
sIBM
but
also
in
PM
,
DM
and
JDM
,
probably
in
response
to
an
exogenous
or
endogenous
'
danger
signal
'
.
However
,
autophagic
activation
and
regulation
,
and
also
interaction
with
the
innate
immune
system
,
differ
in
each
type
of
IIM
.
Better
understanding
of
these
differences
may
lead
to
new
therapies
for
the
different
IIM
types
.
Diseases
Validation
Diseases presenting
"inflammatory myopathies"
symptom
familial mediterranean fever
focal myositis
inclusion body myositis
pyomyositis
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