Signal regulatory protein molecules are differentially expressed, by CD8- dendritic cells

Abstract

A normalized subtracted gene expression library was generated from freshly isolated mouse dendritic cells (DC) of all subtypes, then used to construct cDNA microarrays. The gene expression profiles of the three splenic conventional DC (cDC) subsets were compared by microarray hybridization and two genes encoding signal regulatory protein ? (Sirp?1 and Sirp?4) molecules were identified as differentially expressed in CD8- cDC. Genomic sequence analysis revealed a third Sirp? member localized in the same gene cluster. These Sirp? genes encode cell surface molecules containing extracellular Ig domains and short intracytoplasmic domains that have a charged amino acid in the transmembrane region which can potentially interact with ITAM-bearing molecules to mediate signaling. Indeed, we demonstrated interactions between Sirp?1 and ?2 with the ITAM-bearing signaling molecule Dap12. Real-time PCM analysis showed that all three Sirp? genes were expressed by CD8- cDC, but not by CD8+ cDC or plasmacytoid pre-DC. The related Sirp? gene showed a similar expression profile on cDC subtypes but was also expressed by plasmacytoid pre-DC. The differential expression of Sirp? and Sirp?1 molecules on DC was confirmed by staining with mAbs, including a new mAb recognizing Sirp?1. Cross-linking of Sirp?1 on DC resulted in a reduction in phagocytosis of Leishmania major parasites, but did not affect phagocytosis of latex beads, perhaps indicating that the regulation of phagocytosis by Sirp?1 is a ligand-dependent interaction. Thus, we postulate that the differential expression of these molecules may confer the ability to regulate the phagocytosis of particular ligands to CD8- cDC. Copyright © 2006 by The American Association of Immunologists, Inc.