Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues
2010 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 116, no 18, 3517-3525 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 116, no 18, 3517-3525 p.
IdentifiersURN: urn:nbn:se:umu:diva-41354DOI: 10.1182/blood-2010-03-277244ISI: 000283853200021PubMedID: 20682853OAI: oai:DiVA.org:umu-41354DiVA: diva2:405686