Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) 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; provisionally designated IL-22) is a cytokine with limited homology to IL-10. We report here the identification of a functional IL-TIF receptor complex that consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the second 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 cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional 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-gammaR1 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 expression in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of binding 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 receptor complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the shared use of the gamma common chain (gamma(c)) by several cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15.
Kotenko
S V
SV
Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA. kotenkse@umdnj.edu
Izotova
L S
LS
Mirochnitchenko
O V
OV
Esterova
E
E
Dickensheets
H
H
Donnelly
R P
RP
Pestka
S
S
D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000302:isolation & purification*; D053701:Receptors, Interleukin-10; D015398:Signal Transduction; D000097043:Interleukin-22
D003432:Cross-Linking Reagents; D016207:Cytokines; D007378:Interleukins; D008024:Ligands; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C404815:IL-10-related T cell-derived inducible factor, IL-TIF; C415369:interleukin-22 receptor