| First Author | Saito Y | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 18 | Pages | 3517-25 |
| PubMed ID | 20682853 | Mgi Jnum | J:166657 |
| Mgi Id | MGI:4848294 | Doi | 10.1182/blood-2010-03-277244 |
| Citation | Saito Y, et al. (2010) Regulation by SIRPalpha of dendritic cell homeostasis in lymphoid tissues. Blood 116(18):3517-25 |
| abstractText | The molecular basis for regulation of dendritic cell (DC) development and homeostasis remains unclear. Signal regulatory protein alpha (SIRPalpha), 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 SIRPalpha that lacks the cytoplasmic region. We also found that SIRPalpha is required intrinsically within cDCs or DC precursors for the homeostasis of splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPalpha 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 SIRPalpha 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. SIRPalpha as well as its ligand, CD47, are thus important for the homeostasis of CD4+ cDCs or double negative cDCs in lymphoid tissues. |
