Journal article

Publication year: 1998

Pages: 6871-6877

Journal: The Journal of Immunology

Volume number: 161

Issue number: 12

ISSN: 0022-1767

URL: www.jimmunol.org/content/161/12/6871

Publisher: American Association of Immunologists

Abstract: 
IL-1 binds to two types of receptors on the cell membrane, of which only type I (IL-1RI) transduces signals in concert with the coreceptor IL-1 receptor accessory protein (IL-1RAcP) while type II (IL-1RII) allegedly functions solely as ligand sink and decoy receptor without participating in IL-1 signaling. To investigate the regulatory Role of IL-1RII on IL-1 responsiveness, a chimeric receptor encompassing the extracellular and transmembrane portions of IL-1RII and the cytoplasmic signal-transducing domain of IL-1RI was transfected into two murine EL-4-derived sublines that do or do not express IL-1RAcP, respectively. The chimeric receptor was able to transduce the IL-1 signal and induce IL-2 production only in the cell line which expressed IL-1RAcP, suggesting effective interaction between the extracellular domains of IL-1RII and IL-1RAcP in the presence of IL-1, The physical association of ligated IL-1RII with IL-1RAcP was proven by crosslinking experiments with radio-iodinated IL-l and subsequent immunoprecipitations in normal human B cells and in EL-4 D6/76 cells transiently cotransfected with IL-1RII and IL-1RAcP, respectively. Based on these findings, it is proposed that upon IL-1 binding IL-1RII can recruit IL-1RAcP into a nonfunctional trimeric complex and thus modulate IL-1 signaling by subtracting the coreceptor molecule from the signaling IL-1RI, In this novel mechanism of coreceptor competition, the ratio between IL-1RII and IL-1RI becomes the central factor in determining the IL-1 responsiveness of a cell and the availability of IL-1RAcP becomes limiting for effective IL-1 signaling.

Harvard Citation style: Lang, D., Knop, J., Wesche, H., Raffetseder, U., Kurrle, R., Boraschi, D., et al. (1998) The Type II IL-1 Receptor Interacts with the IL-1 Receptor Accessory Protein: A Novel Mechanism of Regulation of IL-1 Responsiveness, The Journal of Immunology, 161(12), pp. 6871-6877. www.jimmunol.org/content/161/12/6871

APA Citation style: Lang, D., Knop, J., Wesche, H., Raffetseder, U., Kurrle, R., Boraschi, D., & Martin, M. (1998). The Type II IL-1 Receptor Interacts with the IL-1 Receptor Accessory Protein: A Novel Mechanism of Regulation of IL-1 Responsiveness. The Journal of Immunology. 161(12), 6871-6877. www.jimmunol.org/content/161/12/6871