Chronic inflammation is a driver of many lung and airways diseases. A key component of airway inflammation is the cross-talk between the epithelial cells and resident immune cells. Using single cell sequencing and spatial transcriptomics, we identified previously unknown signalling circuits between airway epithelial cells and CD4 T cells via MHCII in healthy human lungs (Madisoon, Oliver et al. Nature Genetics 2023). Extending on these observations, we investigated immune-epithelial cell signalling circuits in asthma, a condition with genetic associations to MHCII-dependent T helper cell genes. We generated single cell sequencing data from CD4 T cells and epithelial cells asthmatics, healthy controls and asthmatics in remission. We observed increased abundance, activation and metabolic profile of tissue resident memory T cells (TRMs) in persistent asthmatics compared with controls. We identify asthma specific signalling patterns between TRMs and epithelial cells which demonstrate an ongoing inflammatory response. To understand the dynamic response of CD4 T cells to epithelial derived signalling during inflammation, we stimulated lung resident T cells with asthma relevant stimuli (anti-CD3/28, + asthma relevant cytokines IL25 or IL33) and profiled with multiome to capture both RNA and open chromatin (ATAC) at the single cell level. The resulting dataset promises to reveal mechanistic insights surrounding the regulatory networks of T cell activation in asthma, with scope to highlight novel therapeutic targets.