Laboratory for Host Defense
Team Leader
Tsuneyasu KAISHO
(M.D., Ph.D.)
Host defense in mammals consists of innate and adaptive immunity. Innate immunity functions as a hard wired pathogen sensor and eradicator. Furthermore, innate immunity contributes both to the establishment and the features of an adaptive immune response. Dendritic cells (DCs) are antigen presenting cells critically involved in regulating these immune responses. DCs sense various pathogen-derived molecules and exert their immunostimulatory functions by producing inflammatory cytokines and/or upregulating expression of costimulatory molecules. The pathogen-derived components, termed immune adjuvants based on their DC activating abilities, are recognized by various types of pattern recognition receptors including Toll-like receptors (TLRs). Identification of new types of immune adjuvants and characterization of the mechanisms by which they activate DCs should contribute to development of novel immunoregulatory strategies. We are attempting to clarify how DCs are activated through pattern recognition receptors and to obtain essential information for effectively manipulating the immune response. Various immune adjuvants, TLR ligands, and gene targeted mice are important tools for this purpose.
- Mechanisms for type I interferon induction in TLR7/9-stimulated dendritic cells
- Mechanisms for regulating dendritic cell subset functions
- April 30, 2007
- Laboratory for Host Defense of RCAI clarified a new regulatory mechanism of innate and adaptive immunity.
- August 17, 2007
- Elucidating the mechanism behind immunity using dendritic cells
- 79. C. Yamazaki, R. Miyamoto, K. Hoshino, Y. Fukuda, I. Sasaki, M. Saito, H. Ishiguchia, T. Yano, T. Sugiyama, H. Hemmi, T. Tanaka, E. Hamada, T. Hirashima, R. Amakawa, S. Fukuharab, S. Nomura, T. Ito, T. Kaisho,
"Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice."
Biochem. Biophys. Res. Commun. 397:756-761. 2010. - K. Hoshino , I. Sasaki , T. Sugiyama , T. Yano , C. Yamazaki , T. Yasui , H. Kikutani, T. Kaisho.
"Cutting edge: Critical role of IkB Kinase a in TLR7/9-Induced type I interferon production by conventional dendritic cells."
J. Immunol 184:3341-3345. 2010. - T. Kaisho and T. Tanaka.
"Turning NF-kB and IRFs on and off in DC."
Trends Immunol. 29:329-336. 2008. - K. Hoshino and T. Kaisho.
"Nucleic acid sensing Toll-like receptors in dendritic cells."
Curr. Opin. Immunol. 20:408-413. 2008. - T. Tanaka, M. J. Grusby and T. Kaisho.
"PDLIM2-mediated termination of transcription factor NF-kappaB activation by intranuclear sequestration and degradation of the p65 subunit."
Nature Immunol. 8(6):584-591. 2007 - K. Hoshino, T. Sugiyama, M. Matsumoto, T. Tanaka, M. Saito, H. Hemmi, O. Ohara, S. Akira, T. Kaisho.
"IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9."
Nature. 440: 949-953. 2006 - H. Hemmi, T. Kaisho, K. Takeda, and S. Akira
"The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets."
J. Immunol. 170: 3059-3064. 2003 - T. Kaisho, K. Hoshino, T. Iwabe, O. Takeuchi, T. Yasui, and S. Akira.
"Endotoxin can induce MyD88-deficient dendritic cells to support Th2 cell differentiation."
Int. Immunol. 14:695-700. 2002 - T. Kaisho, O. Takeuchi, T. Kawai, K. Hoshino, and S. Akira
"Endotoxin-induced maturation of MyD88-deficient dendritic cells."
J. Immunol. 166:5688-5694. 2001 - T. Kaisho, K. Takeda, T. Tsujimura, T. Kawai, F. Nomura, N. Terada, and S. Akira.
"IkappaB kinase alpha is essential for mature B cell development and function."
J. Exp. Med. 193:417-426. 2001
Principal Investigator
- Tsuneyasu KAISHO
- Team Leader
Members
- Katsuaki HOSHINO
- Visiting Scientist
- Hiroaki HEMMI
- Visiting Scientist