Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues.
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.
Saito
Yasuyuki
Y
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
Iwamura
Hiroko
H
Kaneko
Tetsuya
T
Ohnishi
Hiroshi
H
Murata
Yoji
Y
Okazawa
Hideki
H
Kanazawa
Yoshitake
Y
Sato-Hashimoto
Miho
M
Kobayashi
Hisae
H
Oldenborg
Per-Arne
PA
Naito
Makoto
M
Kaneko
Yoriaki
Y
Nojima
Yoshihisa
Y
Matozaki
Takashi
T
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
D039521:CD11c Antigen; D015704:CD4 Antigens; D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic