An immune response network associated with the presence of plasmacytoid dendritic cells in the human atherosclerotic plaque

Purpose: Plasmacytoid dendritic cells (pDCs) play a pivotal role in orchestrating immunity and tolerance, and as such, they are key targets for immunotherapy. It has been shown that pDCs populate the inflamed human atherosclerotic plaque, thus proposing a pro-inflammatory role through release of type I interferons (IFNs). However, a functional role for pDCs in the human plaque is still ambiguous and mouse data available so far show controversial results. Here, we investigated the impact of human plaque pDCs on its local context, applying state of the art genomics. Methods: Using laser capture microdissection, we have isolated pDC-enriched and non-enriched plaque regions from human carotid endarterectomy tissue samples, and performed genome-wide micrarraying. Besides comparing the gene expression patterns between pDC-enriched and non-enriched regions, we have employed network analyses and subsequent module trait correlation analysis to identify and characterize clusters of tightly co-expressed gene modules for macrophages, T cells and vessels, strongly associated with the presence of pDCs. Results: Particularly, coexpression network analysis resulted in a T cell correlated genes module (Figure 1) which led to the identification of five significantly overexpressed immune clusters, representing two major axes: regulation of neutrophil chemotaxis and regulation of T cell proliferation. Moreover, we have been able to identify two miRNAs, miRNA-518A-5P and miRNA-382.5, which target the pDC-T-cell gene cluster. ![Figure][1] Figure 1 Conclusion: Thus, this study has not only revealed a direct cross talk between pDCs and its immune context on the plaque, but also led to the identification of novel central modifiers in pDC mediated immune responses in the lesion. [1]: pending:yes