Allergen Specific Immunotherapy Leads To Multiple Transcriptional Changes In A Peach Allergy Mouse Model

Allergen-specific immunotherapy (IT) induces tolerance in food allergy. Immunological changes during IT have been investigated, however little work has looked at global gene-expression changes. We have developed a tolerance-model of peach allergy using a novel system of sublingual IT (SLIT) based on glycodendropeptides. We analysed changes in dendritic cells (DCs) from mice receiving SLIT. RNA-Seq was used to profile transcriptional changes in lymph node DCs for mice from two groups: anaphylactic mice treated with 2nM SLIT (tolerant), anaphylactic mice treated with 5nM SLIT (desensitized) and two controls: sensitized and anaphylactic mice. Mice were challenged intraperitoneally with Pru p 3, then sacrificed. Poly(A) enriched RNA sequencing was performed using Illumina HiSeq (100bp, paired end); sequences were aligned to the mouse genome using STAR. Differential expression analysis was performed using DESeq2 and functional enrichment analysis using TopGO. Gene expression for the sensitized, desensitized and tolerant mice groups were compared with anaphylactic samples. Sensitized mice showed the largest number of changes, followed by desensitized, then tolerant mice. Nevertheless, there was a set of core genes that changed in all comparisons. In terms of functional enrichment analysis, there was an overrepresentation of genes involved in the innate immune response, regulation of T-cell proliferation and TNF signaling. Interestingly, genes belonging to the MHC-II complex showed altered expression in different groups. By exploring gene expression at the global level we are able to obtain insights into the transcriptional changes and cellular processes that occur during immunotherapy. Future work is needed to further investigate these changes.