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* Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;
MacFarlane Burnet Institute of Medical Research and Public Health, Austin Campus, Heidelberg, Victoria, Australia; and
Kirin Brewery, Tokyo, Japan
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 
(Sirp1 and Sirp4) 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 Sirp1 and 2 with the ITAM-bearing signaling molecule Dap12. Real-time PCR 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 Sirp1 molecules on DC was confirmed by staining with mAbs, including a new mAb recognizing Sirp1. Cross-linking of Sirp1 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 Sirp1 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.
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