イワサキ　マサユキ   Iwasaki Masayuki   岩崎　正幸    所属   研究施設 研究施設    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex.
掲載誌名	正式名：Journal of immunology (Baltimore, Md. : 1950) 略　 称：J Immunol ISSNコード：00221767/00221767
掲載区分	国外
巻・号・頁	167(3),pp.1306-12
著者・共著者	Nakahira M, Tomura M, Iwasaki M, Ahn H J, Bian Y, Hamaoka T, Ohta T, Kurimoto M, Fujiwara H
発行年月	2001/08
概要	IL-12 and IL-18 are both proinflammatory cytokines that contribute to promoting Th1 development and IFN-gamma expression. However, neither IL-12R nor IL-18R is expressed as a functional complex on most resting T cells. This study investigated the molecular mechanisms underlying the induction of an IL-18R complex in T cells. Resting T cells expressed IL-18Ralpha chains but did not exhibit IL-18 binding sites as detected by incubation with rIL-18 followed by anti-IL-18 Ab, suggesting a lack of IL-18Rbeta expression in resting T cells. Although they also failed to express IL-12R, stimulation with anti-CD3 plus anti-CD28 generated IL-12R. Exposure of these cells to IL-12 led not only to up-regulation of IL-18Ralpha expression but also to induction of IL-18R binding sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA expression. The IL-18 binding site represented a functional IL-18R complex capable of exhibiting IL-18 responsiveness. IL-12 induction of an IL-18R complex and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T cells and was substantially decreased in IFN-gamma(-/-) T cells. However, the failure of STAT4(-/-) T cells to induce an IL-18R complex was not corrected by IFN-gamma. These results indicate that STAT4 and IFN-gamma play an indispensable role and a role as an amplifying factor, respectively, in IL-12 induction of the functional IL-18R complex.
DOI	10.4049/jimmunol.167.3.1306
PMID	11466347