Differential gene expression in human tissue resident regulatory T cells from lung, colon, and blood

// Magdalena Niedzielska 1, * , Elisabeth Israelsson 1, * , Bastian Angermann 1 , Benjamin S. Sidders 3 , Maryam Clausen 2 , Matthew Catley 1 , Rajneesh Malhotra 1 and Celine Dumont 1 1 Bioscience, Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden 2 Translational Genomics, Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden 3 Bioscience, Oncology, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, UK * These authors contributed equally to this work Correspondence to: Elisabeth Israelsson, email: Elisabeth.Israelsson@astrazeneca.com Keywords: human regulatory T cell; tissue microenvironment; transcriptome; RNA-seq; mucosal tissue Received: May 16, 2018      Accepted: October 24, 2018      Published: November 16, 2018 ABSTRACT As we learn more about how immune responses occur in situ , it is becoming clear that each organ/tissue is characterized with its own anatomy and microenvironment which may affect and even determine the outcome of the immune responses. With emerging data from animal studies showing that regulatory T cells infiltrating non-lymphoid tissues exhibit unique phenotypes and transcriptional signatures and display functions beyond their well-established suppressive roles, there is an urgent need to explore the function of tissue Treg cells in humans. Here we characterized the transcriptome of Treg residing at the human mucosal tissue obtained from the normal area of cancer resections and their peripheral blood counterparts, identifying human lung and colon tissue Treg signature genes and their upstream regulators. Pathway analysis highlighted potential differences in the cross-talk between tissue Treg cells and other non-immune tissue-specific cell types. For example, genes associated with wnt pathway were differentially regulated in lung Treg cells compared to blood or colon indicating a potential role for lung Treg cells in epithelium repair and regeneration. Moreover, we identified several non-coding RNAs specifically expressed by tissue-resident Tregs. These results provide a comprehensive view of lung and colon tissue Treg transcriptional landscape.