Summary of Research Project Results Under the JSPS FY2000
"Research for the future Program"

1.Research Institution@University of Tokyo
2.Research Area@Life Sciences
3.Research Field@Cellular Signaling
4.Term of Project@FY1996`FY2000
5.Project Number@96L00307
6.Title of Project@Growth and differentiation signalling in the immune system

7.Projetct Leader
Name Institution,Department Title of Position
Tadatsugu Taniguchi University of Tokyo, Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Nobuyuki Tanaka University of Tokyo, Graduate School of Medicine Associate professor
Shinsuke Taki University of Tokyo, Graduate School of Medicine Lecturer
Akinori Takaoka University of Tokyo, Graduate School of Medicine Asistant professor

9.Cooperating Researchers

10.Summary of Research Results

Host cells prevent invasion of pathogens by activating their intrinsic defense systems. These host defense mechanisms are mainly dependent on immune cells including lymphocytes, which are known to differentiate from hematopoietic stem cells. Recently, much attention and efforts have been paid toward the elucidation of mechanism for differentiation and proliferation of these immune cells. However, various issues still remain to be clarified for full understanding of these systems.
In the current study, we analyze cellular signalling and its target genes in immune system for host defense, and reveal molecular mechanisms underlying lymphocyte proliferation and differentiation. As several representative works of the five year-research accomplishments, four major points are noted in this study: We found (1) novel cross-talk mechanisms between RANKL and IFN- as well as between IFN-/ and IFN- receptor components, (2) essential roles of IRF-3 and IRF-7 for IFN-/ gene induction in viral infection, (3) functional role of IRF-2 as a transcriptional attenuator of IFN-/ signalling and (4) identification of Noxa, a novel p53-inducible gene, whose gene product mediate p53-induced apoptosis. On the basis of these results, we provided a new insight into the mechanistic machinery of cellular signalling; crucial roles of constitutive weak signalling for efficient and robust responses in host defense system. Furthermore, we contributed to creating a novel research field, "Osteoimmunology" in this research.
Taken together, we believe that our research accomplishments made progress into the study on cellular signalling for proliferation and differentiation in immune system, and that these results will provide any contributions not only to basic science but also to its application to clinical science.

11.Key Words

(1)Interleukin-2A(2)IRF-family membersA(3)RANKL
(4)InterferonA(5)Signalling cross-talkA(6)Noxa
(7)p53-inducible genesA(8)ApoptosisA(9)Viral infection


[Reference Articles]
Author Title of Article
Takayanagi et al. T cell-mediated regulation of osteoclastogenesis via novel signalling cross-talk between RANKL and IFN-.
Journal Volume Year Pages Concerned
Nature 408 2000 600-605

Author Title of Article
Takaoka et al. Cross talk between interferon- and / signaling components in caveolar membrane domains.
Journal Volume Year Pages Concerned
Science 288 2000 2357-2360

Author Title of Article
Sato et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-/ gene induction.
Journal Volume Year Pages Concerned
Immunity 13 2000 539-548

Author Title of Article
Hida et al. T cell mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-/ signalling.
Journal Volume Year Pages Concerned
Immunity 13 2000 643-655

Author Title of Article
Oda et al. Noxa, a BH3-only member of the Bcl-2 family, and candidate mediator of p53-induced apoptosis
Journal Volume Year Pages Concerned
Science 288 2000 1053-1058