The IL-10 receptor, IL-10R, is a member of the class II subgroup of the cytokine receptor family and exhibits structural similarity to the interferon receptor. IL-10R is expressed in B cells and T helper cells, as well as in LPS-induced mouse fibroblasts. Overall, mouse IL-10R and human IL-10R share 60% sequence identity at the protein level. Stimulation with IL-10 leads to phosphorylation of JAK1 and Tyk 2 tyrosine kinases. The activated kinases phosphorylate the two tyrosine residues (Tyr 446 and Tyr 496) in the cytoplasmic domain of IL-10R?. The phosphorylation of these two residues are required for proper function of IL-10R and activation of IL-10E1 signaling. IL-10R? is ubiquitously expressed and, in addition to forming the IL-10 heterodimeric receptor, it forms a heterodimeric receptor with an IL-22R subunit and an IL-28R subunit. IL-10R is constitutively expressed on human natural killer (NK) cells and the direct binding of IL-10 potentiates cytokine production by human NK cells.