High-throughput sequencing of gluten-specific T cells in celiac disease
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- Institutt for klinisk medisin [10814]
Sammendrag
Celiac disease is a chronic inflammatory disorder resulting from mis-appropriate immune response toward ingested glu-ten proteins. Gluten-specific CD4+ T cells, as the key drivers for the pathogenesis can be identified by staining with HLA-DQ:gluten tetramers. In this project, we conducted single cell transcriptome sequencing on CD4+ T cells sampled from peripheral blood of untreated CD patients. The tetramer-specific T cells showed transcriptomic profiles consistent with activated effector memory T cells that share features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in metabolic processes, including fatty acid metabolism and redox potentials. In addition, we utilized the unique expression of immune receptor of each T and B cell to quantify the impact of index switching on single cell RNA-seq experiments. We also demonstrated that the state of celiac disease could be inferred by unbiased direct TCR sequencing on lamina propria T cells, which is promising for the ultimate goal of inferring celiac disease state based on TCR sequencing of cir-culating T cells.Artikkelliste
Paper I: Ying Yao, Asima Zia, Ralf Stefan Neumann, Milena Pavlovic, Gabriel Balaban, Geir Kjetil Sandve, Shuo-Wang Qiao. T Cell Receptor Repertoire as a Potential Diagnostic Marker for Celiac Disease. Clinical Immunology. 2021 Jan; 222; 108621. doi: 10.1016/j.clim.2020.108621. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.clim.2020.108621 |
Paper II: Ying Yao, Asima Zia, Łukasz Wyrożemski, Ida Lindeman, Geir Kjetil Sandve, Shuo Wang Qiao. Exploiting antigen receptor information to quantify index switching in single-cell transcriptome sequencing experiments. PLoS One. 2018 Dec 5;13(12). doi: 10.1371/journal.pone.0208484. The article is included in the thesis. Also available at: https://doi.org/10.1371/journal.pone.0208484 |
Paper III: Ying Yao, Łukasz Wyrożemski, Knut E. A. Lundin, Geir Kjetil Sandve, Shuo-Wang Qiao. Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq. Manuscript under review. To be published. The paper is not available in DUO awaiting publishing. |