T cell diversity during chronic inflammation

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PROJECT SUMMARY Thymus-derived lymphocytes (T cells) are an essential part of host defense and determine the specificity of the immune response to antigens. The overall goal of this proposal is to examine T cells in a chronic inflammatory condition. Inflammation can be driven by activation of various types of effector T cells or dysregulation of regulatory T cells, however, whether these different subsets of T cells share the same TCR and recognize the same antigen epitope is largely unknown. Furthermore, the link between gene expression and clonal expansion at single cell level has not been established during chronic inflammation in the lung. We plan to perform single- cell RNA sequencing of T cells from the airways of patients with advanced cystic fibrosis (CF) lung disease compared to non-disease controls to fill this knowledge gap. We will use CF as a model to study chronic inflammatory states in the lung. We hypothesize that T cells in the chronically inflamed CF airway have distinctly different transcriptomic profiles compared to non-disease T cells, and using TCR analysis, we postulate increased clonal expansion and Type 17 immunity bias will be observed in CF T cells. Our research aims include: 1) To investigate T cell phenotypes, gene regulatory pathways, and antigenicity within the CF airway and (2) To validate top gene candidates of T cells within the CF airway identified using single-cell RNA sequencing.