Interleukin-10 receptor (IL-10R) is a

type II cytokine receptor Type II cytokine receptors, also commonly known as class II cytokine receptors, are transmembrane proteins that are expressed on the surface of certain cells. They bind and respond to a select group of cytokines including interferon type I, i ...

. The receptor is

tetrameric A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...

, 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 A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

) 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 Type II cytokine receptors, also commonly known as class II cytokine receptors, are transmembrane proteins that are expressed on the surface of certain cells. They bind and respond to a select group of cytokines including interferon type I, i ...

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 A tetrameric protein is a protein with a quaternary structure of four subunits (tetrameric). Homotetramers have four identical subunits (such as glutathione S-transferase), and heterotetramers are complexes of different subunits. A tetrame ...

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 Janus kinase, JAK family that was described (the other members are Janus kinase 1, JAK1, Janus kinase 2, JAK2, ...

kinases. JAK1 associates with the α subunit, and

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 respon ...

, which is additionally phosphorylated by JAK1 and

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 bowel 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

* Type II cytokine receptors {{membrane-protein-stub