| First Author | Cheung H | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 9 | Pages | 5351-7 |
| PubMed ID | 15843532 | Mgi Jnum | J:98417 |
| Mgi Id | MGI:3578455 | Doi | 10.4049/jimmunol.174.9.5351 |
| Citation | Cheung H, et al. (2005) Accessory protein-like is essential for IL-18-mediated signaling. J Immunol 174(9):5351-7 |
| abstractText | IL-18 is an essential cytokine for both innate and adaptive immunity. Signaling by IL-18 requires IL-18Ralpha, which binds specifically to the ligand and contains sequence homology to IL-1R and TLRs. It is well established that IL-1R signaling requires an accessory cell surface protein, AcP. Other accessory proteins also exist with roles in regulating TLR signaling, but some have inhibitory functions. An AcP-like molecule (AcPL) has been identified with the ability to cooperate with IL-18Ralpha in vitro; however, the physiological function of AcPL remains unknown. In this study, we demonstrate that IL-18 signals are abolished in AcPL-deficient mice and cells. Splenocytes from mutant mice fail to respond to IL-18-induced proliferation and IFN-gamma production. In particular, Th1 cells lacking AcPL fail to produce IFN-gamma in response to IL-18. AcPL-deficient neutrophils also fail to respond to IL-18-induced activation and cytokine production. Furthermore, AcPL is required for NK-mediated cytotoxicity induced by in vivo IL-18 stimulation. However, AcPL is dispensable for the activation or inhibition of IL-1R and the various TLR signals that we have examined. These results suggest that AcPL is a critical and specific cell surface receptor that is required for IL-18 signaling. |
