|1.Research Institution||Keio University|
|2.Research Area||Life Sciences|
|3.Research Field||Infectious Diseases and Bioregulation|
|4.Term of Project||FY 1997 〜 FY 2001|
|6.Title of Project||Functional Analysis of Cellular Immunity in Infectious Diseases|
|Name||Institution,Department||Title of Position|
|Shigeo, Koyasu||Keio University, School of Medicine||Professor|
|Names||Institution,Department||Title of Position|
|Yasuo, Ikeda||Keio University, School of Medicine||Professor|
|Hiromichi, Ishikawa||Keio University, School of Medicine||Professor|
|Tsutomu, Takeuchi||Keio University, School of Medicine||Professor|
9.Summary of Research Results
1) Contrary to the current model that interferon-γ (IFN-γ) is during early phase of infection
produced by natural killer (NK) cells in response to IL-12 produced by antigen presenting
cells (APCs) including dendritic cells (DCs) and macrophages, we revealed that
interferon-γ (IFN-γ) is produced by APCs in response to IL-12 produced by themselves
upon microbial infection. It is likely that APCs play a pivotal role in innate immune
responses against microbial infection by producing IFN-γ in an autocrine manner.
2) Using Leishmania major infection, it was demonstrated that a genetic factor(s) determining Th1 vs. Th2 responses against L. major is carried by DCs. Phosphoinositide 3-kinase (PI3K) was shown to be involved in Th1/Th2 regulation.
3) We showed that PI3K is critical in B cell development and functions. Furthermore, we demonstrated that PI3K is essential for the development of gastrointestinal mast cells and immunity against intestinal nematode infection.
4) We identified "cryptopatches" in both small and large intestines, as anatomical sites for differentiation of intestinal intraepithelial lymphocytes in the gut. Each cryptopatch contains 〜1000 c-kit+ progenitor cells that are capable of differentiating into T cells.
(1)microbial infection、(2)innate immunity、(3)dendritic cell
(4)interferon-γ、(5)type-1 helper T cell、(6)type-2 helper T cell
(7)mast cell、(8)intestinal intraepithelial cell、(9)knockout mouse