Exploring full-length T cell receptor sequencing and CITE-Seq to identify and characterize pathogenic T cells in psoriasis 3314

Abstract Description Psoriasis is a chronic autoimmune condition characterized by rapid skin cell buildup and significant systemic inflammation. In psoriasis, subsets of memory T cells exhibit a distinct phenotype marked by the expression of cutaneous lymphocyte antigen (CLA) and chemokine receptors that allow them to recirculate. Because circulating CLA+ T cells are biomarkers for psoriasis and other skin inflammatory conditions, we sought to examine the relationship between memory T cells derived from skin (CLA+) and other T cells (CLA-) using a multiomic approach that included TCR sequencing. Using the BD FACSDiscoverTM Imaging Cell Sorter, we confirmed CLA+ cell expansion in psoriasis and observed that CD8 T cells but not CLA+CD4+ T cells secreted IFNg in response to TCR stimulation. Strikingly, full-length TCR sequencing of over 60,000 memory single T cells from six individuals revealed 263 shared clonotypes between CLA- and CLA+ memory CD8 T cells. Cellular indexing of transcriptomes and epitopes (CITE-Seq) analysis showed that CLA-CD8+ T cells responded to TCR stimulation by upregulating type I IFN-related genes, suggesting they may drive antigen-specific inflammation beyond the skin, while CLA+ clonotypes showed signs of exhaustion. Our findings show the value of full-length TCR sequencing for exploring skin-trained memory T cells, offering insights into immune processes and aiding in the development of targeted therapies without the need for skin biopsies. Topic Categories Immune Mechanisms of Human Disease (HUM)