Transcriptional profiling of dendritic cells in a mouse model of food-antigen induced anaphylaxis reveals the upregulation of multiple immune-related pathways.

Abstract

Scope Much of our knowledge about gene expression during anaphylaxis comes from candidate gene studies. Despite their potential role, expression changes in dendritic cells (DCs) have not been studied in this context using high throughput methods. We investigated the molecular mechanisms underlying food-antigen induced anaphylaxis using DCs from an animal model. Methods and results We used RNA sequencing to study gene expression in lymph node derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3, during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least two-fold changes. Almost three quarters of these increased during anaphylaxis. A subset was confirmed using RT-PCR in a second set of samples obtained from a new batch of mice. Enrichment analysis showed an overrepresentation of genes involved in key immune system and inflammatory processes including TGF-β signalling. Comparison with a study using anaphylactic human subjects showed significant overlap. Conclusions Our findings provide a comprehensive overview of the transcriptional changes occurring in DCs during anaphylaxis and help elucidate the mechanisms involved. They add further weight to the putative role of these cells in anaphylaxis and highlights genes that may represent potential therapeutic targets.