Relationships Among Murine CD11c~(high) Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns

摘要

The functional relationships and properties of different substypes of dendritic cells (DC) remain largely undefined. To better characterize these cells, we used global gene analysis to determine gene expression patterns among murine CD11c~(high) DC subsets. CD4~+, CD8alpha~-CD4~- (double negative (DN)) DC were purified from spleens of norml C57/BL6 mice and analyzed using Affmetrix microarrays. The CD4~+ and CD8alpha~+ Dcsubsets showed distinct basal expression profiles differing by > 200 individual genes. These included known DC subset markers as well as previously unrecognized, differentially expressed DC Ags such as CD1d, CD5, CD22, and CD72. Flow cytometric analysis confirmed differential expression in nine of nine cases, thereby validating the microarray analysis. Interestingly, the microarray expression profiles for DN cells strongly resembled those of CD4~+ DC, differing from them by >25 genes. This suggests that CD4~+ and DN DC are closely related phylogenetically, whereas CD8alpha~+ DC represent a more distant lineage, supporting the historical distinction between CD8alpha~+ CD8alpha~- DC. However, staining patterns revealed that in contrast to CD4~+ DC, the DN subset is heterogeneous and comprises at least two subpopulations. Gene Ontology and literature mining analyses of genes expressed differentially among DC subset indicated strong associations with immune response parameters as well as cell differentiation and signaling. Such association offer clues to possible unique functions of the CD11c~(high) DC subsets that to date have been difficult to define as rigid distinctions.