Transcriptomic changes associated with oral immunotherapy for food allergy

This review summarizes recent advances in characterizing the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarize current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitization and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimize treatments and gain improved outcomes for patients. In this review we summarise current understanding of immune changes associated with oral immunotherapy (OIT), as established through molecular profiling of the transcriptome. Changes observed during OIT include clonal anergy of T cells with a Th2 phenotype and decreased expression of Th2 genes in peanut reactive T cells. Demethylation of the FOXP3 locus in T regulatory cells has been demonstrated, correlating with treatment outcome. Decreased frequencies of gamma delta T cells have been observed early on in OIT, which may contribute to the loss of Th2 dominance. Multiple single cell studies of CD4+ T cell memory responses have identified a novel subset of a T-helper cells that express type I interferon stimulated genes and may also act to supress Th2.image