Identification of the functional interleukin-22 (IL-22) receptor complex -The IL-10R2 chain (IL-10R beta) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes

Interleukin-10 (IL-10)-related T cell-derived inducible factor (IL-TIF; pro visionally designated IL-22) is a cytokine with limited homology to IL-10, We report here the identification of a functional IL-TIF receptor complex t hat consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the sec ond chain of the IL-10 receptor complex. Expression of the CRF2-9 chain in monkey COS cells renders them sensitive to IL-TIF, However, in hamster cell s both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functi onal IL-TIF receptor complex. The CRF2-9 chain (or the IL-TIF-R1 chain) is responsible for Stat recruitment. Substitution of the CRF2-9 intracellular domain with the IFN-gamma R1 intracellular domain changes the pattern of IL -TIF-induced Stat activation. The CRF2-9 gene is expressed in normal liver and kidney, suggesting a possible role for IL-TIF in regulating gene expres sion in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of bindin g IL-TIF independently and can be cross-linked to the radiolabeled IL-TIF, However, binding of IL-TIF to the receptor complex is greater than binding to either receptor chain alone. Sharing of the common IL-10R2 chain between the IL-10 and IL-TIF receptor complexes is the first such case for recepto r complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the sha red use of the gamma common chain (gamma (c)) by several cytokines, includi ng IL-2, IL-4, IL-7, IL-9, and IL-15,