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My name is Angel Lopez and
I'm here with my colleague,
Dr. Timothy Hercus who's to
talk about the Beta common
family of cytokines.
They are receptors and ligands.
We are both in the Division of Human
Immunology at the Center for Cancer Biology of
SA Pathology in
Adelaide, Australia.
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The Beta common is the
shared receptor subunit of
a family of cytokines is
the common subunit of
heterodimeric receptors that
comprise an Alpha chain that
binds specifically to
the cognate ligands
and Beta common which is,
as I said is shared amongst
the three receptors.
The three receptors
are those for
granulocyte macrophage
colony stimulating factor
which we refer to as GM-CSF
and two interleukins,
interleukin 3 or IL-3 and
interleukin 5 or IL-5.
These cytokines engage
the receptors and exert
multiple overlapping and
redundant biological functions.
The function probably
the most important
one is the survival.
This function is activated
throughout.
The life of a given cell.
But these cytokines can also
promote the proliferation of
the early progenitor cells
and making them divide.
As they divide they also
differentiate into the mature
progeny of myeloid cells
that we see in
peripheral blood.
Once in the blood these
cells can still be
activated further by GM-CSF,
IL-3 or IL-5 in this case
the cytokines causing
activation of myeloid cells.
In this way they can
more readily and more
effectively kill
invading pathogens.
They can also migrate to
sites of inflammation
where they are
required to clear
a given infection.
Typically these cytokines
display considerable
functional redundancy
so that survival, proliferation,
differentiation
and activation is
mediated by the three cytokines.
Each one of them can promote
these four functions.
Now although the cytokines
are very effective
in vitro and in vivo
to promote the production of
blood cells in particular
myeloid cells.
They don't seem to be
critical for steady-state
hemopoiesis.
In other words, if these cytokines
are eliminated one by one
by gene technology approaches.
They are knockouts for
GM-CSF or for IL-3 or IL-5.
There's no major disruption
of steady-state hemopoiesis.
Normal hemopoiesis
proceed as normal,
perhaps an exception is IL-5
where lack of IL-5 causes
a significant decrease
in the normal levels of
eosinophils, it's a decrease
of about 90 percent.
But the other lineages such
as neutrophils and monocytes,
etc don't seem to be
affected in a big way.
Instead, the way we
see these cytokines at
the moment is as being
important for
reactive hemopoiesis.
In other words, in response
to an outside stimulus,
an injury or an insult
the cytokines are
produced in the body and
then the elevation in
the blood and in the bone marrow
it stimulates the production of
myeloid cells to come
up in the blood so
that we can then see elevated
number of neutrophils.
That's neutrophilia an
elevated number of monocytes
and eosinophilia which is
an elevated number
of eosinophils.
By the type of cell
that is elevated will
depend very much on the type
of cytokine that
is being produced.
The best example is IL-5,
where elevation of IL-5
will give rise to almost
exclusively the number of
eosinophils in peripheral blood.
Now the fact that
these cytokines
have overlapping
activities makes it easy
to understand that
they respond to
a common receptor
organization theme.
In essence, the fact
that Beta common is
shared by the three
receptors goes a long way
to explain why the
three cytokines
can stimulate pretty
much the same functions,
the main difference
being the type
of cells that is
stimulated in each case.
This in turn depends on
the particular receptor that
is expressed on
the cell surface.
For example, eosinophils
will express
all three receptors
IL-5, IL-3 and GM-CSF.
However, other cell types like
neutrophils will
express only GM-CSF.
In this case the production
of GM-CSF will give
rise to neutrophils
and monocytes.
But neutrophils do not
respond well to IL-3 or IL-5.
