Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling.

We have identified a novel member of the interleukin-1 (IL-1) receptor family, which we have termed AcPL. In transient transfection assays, we were unable to demonstrate a role for AcPL in IL-1-induced activation of NFkappaB. Interleukin-18 (interferon-gamma-inducing factor) is another member of the IL-1 family of cytokines, and it has recently been shown that IL-18 has a weak affinity for IL-1R-rp1. We examined whether AcPL might function alone or in concert with IL-1R-rp1 to mediate IL-18 signaling. We found that both IL-1R-rp1 and AcPL expression were required for induction of NFkappaB activity and for activation of c-Jun N-terminal kinase in response to IL-18. Furthermore, a dominant negative version of AcPL specifically inhibited IL-18 signaling. In vitro immunoprecipitation assays demonstrated that AcPL alone was unable to bind IL-18 with any appreciable affinity. We propose that although IL-1R-rp1 binds the cytokine, IL-1R-rp1 and AcPL proteins are both required for IL-18 signaling, analogous to the requirement for both IL-1R and IL-1RAcP in IL-1-mediated responses.