IL-10 Receptor

de Waal Malefyt R.

IL-10 interacts with its tetrameric receptor complex consisting of two IL-10R♂ and two IL-10R♀ chains resulting in the phosphorylation and activation of JAK1 and TYK2 kinases, which in turn phosphorylate two tyrosine residues in the intracytoplasmic parts of the IL-10R♂ chains that form docking sites for STAT3. Binding of STAT3 results in phosphorylation by JAK1 and TYK2 kinases, homo- or heterodimerization and translocation to the nucleus where it binds to the promoters of IL-10-responsive genes such as the FcRI and activates transcription. All IL-10-mediated responses are dependent on activation of STAT3, but the anti-inflammatory actions of IL-10 require additional sequences in the distal intracytoplasmic part of the IL-10R♂ chain.