T-cell instructed monocyte activation is a key pathological feature in Ankylosing Spondylitis and provides novel therapeutic opportunities

Activated T-cells potently stimulated monocytes from patients with AS to produce IL-1ß and IL-23. These in turn act back on T cells to enhance Th17 responses. T-cell activated monocytes are heterogeneous but include a subset of “super proinflammatory monocytes” not induced by LPS activation and for enriched for AS risk genes, including ERN1. Importantly, we identify a population of CD14+ myeloid cells highly enriched in AS synovial fluid strikingly similar gene expression profile high levels of CCL3, CCL4, IL1B, TNF, CXCL2, strongly suggesting T cell activation in vivo. a T-cell instructed monocyte activation can be inhibited by genetic or chemical suppression of ERN1. Overall design: PBMCs isolated from AS blood were treated with LPS, T cell activation beads, or no treatment. Cells were then profiled by 10X scRNA-seq