title: Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen.
abstract: The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein α (SIRPα), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell-cell signaling by interacting with CD47, another Ig superfamily protein. In this study, we show that the size of the T cell zone as well as the number of CD4(+) T cells were markedly reduced in the spleen of mice bearing a mutant (MT) SIRPα that lacks the cytoplasmic region compared with those of wild-type mice. In addition, the expression of CCL19 and CCL21, as well as of IL-7, which are thought to be important for development or homeostasis of the T cell zone, was markedly decreased in the spleen of SIRPα MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRPα is important for development of the T cell zone as well as the expression of CCL19 and CCL21 in the spleen. The expression of lymphotoxin and its receptor, lymphotoxin β receptor, as well as the in vivo response to lymphotoxin β receptor stimulation were also decreased in the spleen of SIRPα MT mice. CD47-deficient mice also manifested phenotypes similar to SIRPα MT mice. These data suggest that SIRPα as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen.
authors.affiliation: Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Sato-Hashimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwamura
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kaneko
authors.forename: Shinya
authors.initials: S
authors.lastname: Kusakari
authors.forename: Takenori
authors.initials: T
authors.lastname: Kotani
authors.forename: Munemasa
authors.initials: M
authors.lastname: Mori
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D048429:Cell Size; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D008024:Ligands; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic