Single-cell sequencing reveals a clonal expansion of pro-inflammatory synovial CD8 T cells expressing tissue homing receptors in psoriatic arthritis

Frank Penkava, Martin Del Castillo Velasco-Herrera, Matthew D Young, Nicole Yager, Alicia Lledo Lara, Charlotte Guzzo, Ash Maroof, Lira Mamanova, Suzanne Cole, Mirjana Efremova, Davide Simone, Chrysothemis C Brown, Andrew L Croxford, Sarah Teichmann, Paul Bowness, Sam Behjati, M Hussein Al-Mossaw

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Received Date: 6th August 19

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis.  We used three complementary single cell approaches to study leukocytes from PsA joints. Mass cytometry (CyTOF) demonstrated marked (>3 fold) expansion of memory CD8 T cells in the joints compared to matched blood. Further exploration of the memory CD8 compartment using both droplet and plate based single cell RNA sequencing of paired alpha and beta chain  T cell receptor sequences identified pronounced CD8 T cell clonal expansions within the joints, strongly suggesting antigen driven expansion.  These clonotypes exhibited distinct gene expression profiles including cycling, activation, tissue homing and tissue residency markers. Pseudotime analysis of these clonal CD8 populations identified trajectories in which tissue residency can represent an intermediate developmental state giving rise to activated, cycling and exhausted CD8 populations. Comparing T-cell clonality across patients further revealed specificity convergence of clones against a putative common antigen. We identify chemokine receptor CXCR3 as upregulated in expanded synovial clones, and elevation of two CXCR3 ligands, CXCL9 and CXCL10, in PsA synovial fluid.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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