title: Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues.
abstract: The molecular basis for regulation of dendritic cell (DC) development and homeostasis remains unclear. Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is predominantly expressed in DCs, mediates cell-cell signaling by interacting with CD47, another immunoglobulin superfamily protein. We now show that the number of CD11c(high) DCs (conventional DCs, or cDCs), in particular, that of CD8-CD4+ (CD4+) cDCs, is selectively reduced in secondary lymphoid tissues of mice expressing a mutant form of SIRPα that lacks the cytoplasmic region. We also found that SIRPα is required intrinsically within cDCs or DC precursors for the homeostasis of splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPα mutant mice into DCs induced by either macrophage-granulocyte colony-stimulating factor or Flt3 ligand in vitro was not impaired. Although the accumulation of the immediate precursors of cDCs in the spleen was also not impaired, the half-life of newly generated splenic CD4+ cDCs was markedly reduced in SIRPα mutant mice. Both hematopoietic and nonhematopoietic CD47 was found to be required for the homeostasis of CD4+ cDCs and CD8-CD4- (double negative) cDCs in the spleen. SIRPα as well as its ligand, CD47, are thus important for the homeostasis of CD4+ cDCs or double negative cDCs in lymphoid tissues.
authors.affiliation: Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kaneko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Miho
authors.initials: M
authors.lastname: Sato-Hashimoto
authors.forename: Hisae
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D039521:CD11c Antigen / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D051928:CD47 Antigen / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D015704:CD4 Antigens; D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic