144
Cytokines: Interleukins
4.23
Interleukin-23
IL-23, produced mainly by macrophages
and
dendritic
cells,
is
a
novel
het-
erodimeric cytokine constituted by the p40
subunit of IL-12 and a p19 subunit that is
most closely related to the p35 subunit of
IL-12. It is evident that IL-23, besides shar-
ing one structural subunit with IL-12, also
shares IL-12R
β
1 of the high-afFnity IL-
12R as part of IL-23R. However, a second
speciFc IL-23R component is indicated for
the recognition of p19 suggesting IL-23
has distinct cell targets from IL-12. ±or
instance, although IL-23 in common with
IL-12 stimulates I±N
γ
production, IL-23 is
a strong inducer of memory T-cell prolif-
eration, while IL-12 is not. In addition,
IL-23, in contrast to IL-1, for example,
appears to act more broadly as an end-
stage effector cytokine via direct actions on
macrophages.
4.24
Interleukin-24
IL-24, one of several IL-10 paralogs, for-
merly known as melanoma differentiation-
associated antigen 7 (MDA7), was origi-
nally found to be expressed in differen-
tiated melanoma cells, but is now also
known to be expressed by a variety of cell
types, including T lymphoblasts. IL-24 ap-
pears to act through IL-20R and thus is
expected to have similar cell targets to
IL-20. It has been demonstrated to have
antiproliferative activity against cultured
tumor cell lines, including those derived
from melanomas.
4.25
Interleukin-25
IL-25, also known as S±20, is a novel
cytokine belonging to the IL-17 family,
wh
ichisma
in
lyproducedbyTh2ce
l
ls
.I
t
has been shown to induce expression of
the immunosuppressive interleukins, IL-
4, IL-5 and IL-13, required for Th2-like
responses and may thus be an important
mediator of allergic disease.
4.26
Interleukin-26
IL-26, one of several IL-10 paralogs, also
previously known as AK155, is expressed at
high levels in activated T cells, monocytes,
and various T-derived leukemic cell lines.
However, little is yet known about its cell
targets and biological activities.
4.27
Interleukin-27
IL-27 is a newly identiFed ‘‘IL-12-like’’
heterodimeric cytokine, also similar to
IL-23. It is constituted by Epstein–Barr
virus-induced gene 3 (EBI3) protein, a
protein that is widely expressed and related
to IL-12 p40 subunit and a further homolog
of IL-12 p35 known as p28. IL-27 is the
product
of
activated
antigen-presenting
cells (macrophages and dendritic cells)
and stimulates the rapid clonal expansion
of na¨
ıve but not memory CD4
+
T cells.
It also strongly synergizes with IL-12 to
trigger I±N
γ
production by na¨
ıve CD4
+
T cells.
4.28
Interleukin-28
IL-28 consists of two near identical pro-
teins, IL-28A and B, which are distantly
related to both the IL-10 and I±N
α
fami-
lies, which are induced by viral infection.
They interact with a heterodimeric class
II cytokine receptor that consists of IL-
10R
β
chain and an orphan class II receptor
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