Interleukin-10 receptor (IL-10R) is a
type II cytokine receptor. The receptor is tetrameric, composed of 2
α and 2
β subunits. The
α subunit (encoded in the ''Il10ra gene)'' is expressed on haematopoietic cells (such as T, B, NK, mast, and
dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
) whilst the
β subunit (encoded in the ''Il10rb gene'') is expressed ubiquitously. The
α subunit is exclusive to
interleukin-10, however the
β subunit is shared with other
type II cytokine receptors such as
IL-22R,
IL-26R and INFλR.
The IL-10R
α subunit acts as the ligand binding site and may be upregulated in various cell types as necessary. The IL-10R
β functions as the signaling subunit and is constitutively expressed in a majority of cell types.
There is evidence that upon ligand binding at the
α subunit, a conformational change occurs in the
β subunit that allows it to additionally bind to
IL-10. This structure forms a heterotetramer that leads to the signaling complex activation of
JAK1 and
TYK2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the ''TYK2'' gene.
Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α ...
kinases.
JAK1 associates with the
α subunit, and
TYK2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the ''TYK2'' gene.
Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α ...
with the
β subunit where they then phosphorylate portions of the
α subunit. This recruits
STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family.
Function
STAT3 is a member of the STAT protein family. In respons ...
, which is additionally phosphorylated by
JAK1 and
TYK2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the ''TYK2'' gene.
Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α ...
.
STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family.
Function
STAT3 is a member of the STAT protein family. In respons ...
homodimerizes, moves to the cellular nucleus, and activates gene transcription.
The
Interleukin-10 receptor is implicated in regulation of gastro-intestinal immune response, primarily in the mucosal layer. Murine studies of test subjects lacking functional receptors showed rapid onset of bowl inflammatory disorders. In human studies, the early onset of irritable bowel disease has been correlated with defects in the IL-10R subunits. Cases involving both the
α and
β subunits were identified, some possessing fully dysfunctional receptors, and others being incapable of accepting phosphorylation.
References
External links
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Type II cytokine receptors
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