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interleukin-11 receptor (IL11R) 409 interleukin 12 receptor (IL12R)
gene encoding IL11 are composed of five exons and four
introns. The gene is located at band 19q13.3–13.4 on the
long arm of chromosome 19. It may facilitate plasmacytoma
establishment, possibly representing an important role for
IL11 in tumorigenesis. In combination with IL3, IL11 can
potentiate megakaryocyte growth, producing increased
numbers, sizes, and ploidy values. It may be important in
the formation of platelets. In the presence of functional T
lymphocytes, IL11 can stimulate the production of B cells
that secrete immunoglobulin G (IgG). It has a synergistic
effect in primitive hematopoietic cell proliferation that is
IL3-dependent. IL11 belongs to the IL6 superfamily. It
facilitates platelet recovery after chemotherapy-induced
thrombocytopenia, induces acute phase proteins, modulates
antigen–antibody responses, participates in the regulation
of bone cell proliferation and differentiation, and may be
used as a therapeutic agent for osteoporosis. Apart from its
lymphopoietic, hematopoietic, and osteotrophic properties,
it functions in numerous tissues including brain, intestines,
and testes. It facilitates growth of selected lymphocytes and
in mouse studies has been shown to promote cortical thickness
and strength of long bones. The IL11 receptor (IL11R)
is composed of at least one ligand-binding subunit (IL11Rα)
and a signal transduction subunit (gp130). The murine and
human IL11R cDNAs encode 432- and 422-amino acid
polypeptides, respectively, with two potential N-linked
glycosylation sites and four cysteine residues in the extracellular
domain. IL11Rα is believed to be a member of the
hematopoietin receptor superfamily. Murine and human
IL11Rα have 84% homology at the amino acid level and
85% homology at the nucleotide level.
interleukin-11 receptor (IL11R)
IL11R is composed of at least one ligand-binding subunit
(IL11Rα) and a signal transduction subunit (gp130). Murine
and human IL11R cDNAs encode 432- and 422-amino acid
polypeptides, respectively, with two potential N-linked
glycosylation sites and four cysteine residues in the extracellular
domain. IL11Rα is believed to be a member of the
hematopoietin receptor superfamily. Murine and human
IL11Rαs have 84% homology at the amino acid level and
85% homology at the nucleotide level.
interleukin-12 (IL12)
Comprised of a bundle of four α helices, interleukin-12 is
a heterodimeric cytokine encoded by two separate genes,
IL12A(p35) and IL12B(p40). The active heterodimer and
a homodimer of p40 are generated following protein synthesis.
The molecule is composed of 35-kDa and 40-kDa
chains linked by disulfide bonds. IL12 participates in the
differentiation of naïve T cells into Th1 cells that play a
significant role in resistance against pathogens. It acts on T
cells as a cytotoxic lymphocyte maturation factor (CLMF).
As a T cell-stimulating factor, it can activate the growth and
function of T cells. It also serves as a natural killer (NK)
cell stimulatory factor (NKSF). It induces the synthesis of
IFN-γ and tumor necrosis factor-α (TNF-α) from T and NK
cells and diminishes IL4-mediated suppression of IFN-γ.
IL12 is a growth factor for activated CD4 + and CD8 + T
lymphocytes and for NK cells. It facilitates NK cell and
LAK cell lytic action exclusive of IL2. It can induce resting
peripheral blood mononuclear cells to form IFN-γ in vitro.
IL12 may act synergistically with IL2 to increase responses
by cytotoxic lymphocytes. T cells that synthesize IL12
Interleukin-12 crystal structure.
have CD30 coreceptors associated with IL12 activity. IL12
may have potential as a therapeutic agent in the treatment
of tumors or infections, especially if used in combination
with IL2. IL12 promotes IFN-γ formation by NK cells and
T cells, enhances the cytolytic activity of NK cells and
CTLs, and facilitates the development of Th2 cells. IL2 and
signal transduction of IL12 in NK cells appear to be linked.
IL2 induces the expression of two IL12 receptors, IL12Rβ 1
and IL12β 2, maintaining the expression of a critical protein
associated with IL12 signaling in NK cells. IL12 reveals an
antiangiogenic property by increasing synthesis of IFN-γ,
which increases the formation of a chemokine known as
inducible protein 10 (IP-10 or CXCL 10) that mediates the
antiangiogenic effect. IL12 receptor is designated IL12R.
Two receptor chains, IL12Rβ1and IL12Rβ2, have been
identified and cloned. Both β1 and β2 chains are members
of the cytokine receptor superfamily. They are related to
gp130 of the IL6R and to the receptors of LIF and G-CSF.
Coexpression of both these receptors confers IL12 responsiveness.
Both human- and mouse-activated T cells have
IL12 binding sites of high, intermediate, and low affinities.
IL12Rβ2 has a key role in IL12 function because it is
present on activated T cells and is induced by cytokines
that facilitate Th1 cell development and inhibited by those
that promote Th2 cell development. Following binding,
IL12Rβ2 becomes tyrosine phosphorylated and provides
binding sites for kinases, Tyk2 and Jak2, that are significant
in activating critical transcription factor proteins such as
STAT4 that are involved in IL12 signaling in T cells and
NK cells. This is known as the JAK-STAT pathway. IL12 is
associated with autoimmunity. Its administration to autoimmune
disease patients worsens their condition, possibly
associated with its prominent role in the induction of Th1
immune responses. By contrast, administration of anti-IL12
antibodies to mice and studies in IL12 gene knockout mice
revealed diminished autoimmune responses.
interleukin 12 receptor (IL12R)
Two receptor chains, IL12Rβ 1 and IL12Rβ 2, have been identified
and cloned. Both β 1 and β 2 chains are members of the
cytokine receptor superfamily. They are related to gp130 of
the IL6R and to receptors of LIF and G-CSF. Coexpression
of both these receptors confers IL12 responsiveness. Both
human- and mouse-activated T cells have IL12 binding sites
of high, intermediate, and low affinities.
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