Gopal Krishna Ramadas Dhondalay PhD

Project | 19

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Gastrointestinal γδ T cells reveal differentially expressed transcripts and enriched pathways during peanut oral immunotherapy

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Summary

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Oral immunotherapy (OIT) has been successful in desensitising patients to offending food allergens, although identification of tissue-resident T cell subsets and cognate pathways leading to desensitisation has been challenging. The γδ T cells are a major T-cell subset of mucosal intraepithelial lymphocytes (IELs) and play a significant role in tissue homeostasis and repair. In the broader context of atopy, γδ T cells have been implicated both in IgE and Th2-enhancing as well as IgE-suppressive effects. However, specifically with regards to peanut allergy, γδ T cells were shown to be IgE-suppressive and thus protective in a study employing mouse models. To our knowledge, the role of γδ T cells in the intestinal mucosa of FA patients during immunotherapy has not been examined. To this end, we investigated whether γδ T cells in the gastrointestinal (GI) tract exhibited changes during peanut OIT. We hypothesised that GI-resident γδ T cells in FA patients would increase during the course of peanut OIT and might reveal transcripts and pathways relevant to the mechanisms of peanut desensitisation. To prove our hypothesis, we performed RNA-seq on the isolated γδ T cells from the patients. The sequencing reads were evaluated for quality check by FastQC, and differential expression analysis by DESeq2 was performed. The bioconductor packages pathfindR, kegg and pathview were used for gene-set enriched pathway analysis. Pathways predicted by pathfindR with the Benjamini adjusted P-value < 0.1 were considered as significantly enriched.

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A publication  in the journal of Allergy was published related to this project.​