Identification and functional characterization of a second chain of the interleukin-10 receptor complex

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Abstract
Interleukin‐10 (IL‐10) is a pleiotropic cytokine which signals through a specific cell surface receptor complex. Only one chain, that for ligand binding (IL‐10Rα or IL‐10R1), was identified previously. We report here that, although human IL‐10 binds to the human IL‐10R1 chain expressed in hamster cells, it does not induce signal transduction. However, the co‐expression of CRFB4, a transmembrane protein of previously unknown function belonging to the class II cytokine receptor family, together with the IL‐10R1 chain renders hamster cells sensitive to IL‐10. The IL‐10:CRFB4 complex was detected by cross‐linking to labeled IL‐10. In addition, the IL‐10R1 chain was able to be co‐immunoprecipitated with anti‐CRF antibody when peripheral blood mononuclear cells were treated with IL‐10. These results demonstrate that the CRFB4 chain is part of the IL‐10 receptor signaling complex. Thus, the CRFB4 chain, which we designate as the IL‐10R2 or IL‐10Rβ chain, serves as an accessory chain essential for the active IL‐10 receptor complex and to initiate IL‐10‐induced signal transduction events.