title: Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice.
abstract: The class IV semaphorin Sema4A provides a costimulatory signal to T cells. To investigate the possible developmental and regulatory roles of Sema4A in vivo, we generated Sema4A-deficient mice. Although Sema4A-deficient mice develop normally, DCs and T cells from knockout mice display poor allostimulatory activities and T helper cell (Th) differentiation, respectively. Interestingly, in addition to its expression on DCs, Sema4A is upregulated on Th1-differentiating cells, and it is necessary for in vitro Th1 differentiation and T-bet expression. Consequently, in vivo antigen-specific T cell priming and antibody responses against T cell-dependent antigens are impaired in the mutant mice. Additionally, Sema4A-deficient mice exhibit defective Th1 responses. Furthermore, reconstitution studies with antigen-pulsed DCs reveal that DC-derived Sema4A is important for T cell priming, while T cell-derived Sema4A is involved in developing Th1 responses. Collectively, these results indicate a nonredundant role of Sema4A not only in T cell priming, but also in the regulation of Th1/Th2 responses.
authors.affiliation: Department of Molecular Immunology and CREST Program of JST, Research Institute for Microbial DiseasesOsaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Shikina
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yukawa
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kashiwamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Midori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Ko-Mitamura
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Satoko
authors.initials: S
authors.lastname: Marukawa
authors.forename: Isao
authors.initials: I
authors.lastname: Ishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morishita
authors.forename: Durbaka V R
authors.initials: DV
authors.lastname: Prasad
authors.forename: Manabu
authors.initials: M
authors.lastname: Tamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizui
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toyofuku
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D018390:Gene Targeting; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D039961:Semaphorins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D039961:Semaphorins