The distinct function and control of regulatory T cell subsets during influenza infection

During influenza infection, Treg cells in the lung acquire at least 3 discernable phenotypes which can be characterized by the expression of the IL-33 receptor ST2, the Th1 associated chemokine receptor CXCR3 or neither receptor. It is known in the Treg field that Treg cell acquire different phenotypes to more specifically target related immune responses. For example, Th1 like CXCR3 expressing Treg cells are thought to traffic to and specifically suppress adaptive type 1 immune responses. We have found that during influenza infection, ST2+ Treg cells specifically target innate immune responses characterized by IL-1 mediated neutrophil and eosinophil recruitment and the activation of IL17 producing gamma delta T cells. In order to determine how ST2+ Treg cell perform their specific immunomodulatory function, we have performed RNAseq transcriptomic analysis to compare gene expression in ST2+ Tregs isolated from day 7 influenza infected lungs with CXCR3+ Treg cells and Treg cells expressing neither marker also from day 7 of influenza infected lungs as well as compared to total Treg cells from the spleen of uninfected mice. Overall design: Distinct populations of ST2+, CXCR3+ and ST2-CXCR3- Treg cells (Viable, CD3+, CD4+, YFP+) were sorted from the lungs of day 7 influenza infected Foxp3YFPCre mice. In addition Treg cells (Viable, CD3+, CD4+, YFP+) from the spleens of naïve Foxp3YFPCre mice were also isolated. These cells were then subjected to RNAseq transcriptomic analysis.