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.

DOI: 10.1182/blood-2010-03-277244
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@article{Saito2010RegulationBS, title={Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues.}, author={Yasuyuki Saito and Hiroko Iwamura and Tetsuya Kaneko and Hiroshi Ohnishi and Yoji Murata and Hideki Okazawa and Yoshitake Kanazawa and Miho Sato-Hashimoto and Hisae Kobayashi and Per-Arne Oldenborg and Makoto Naito and Yoriaki Kaneko and Yoshihisa Nojima and Takashi Matozaki}, journal={Blood}, year={2010}, volume={116 18}, pages={3517-25} }