Neuro-immune interactions in chronic joint pain: how T cell subsets might affect persistent nociception in inflammatory arthritis

Improved standard of care has alleviated the inflammatory burden for many patients with inflammatory arthritis (IA). However, the remaining pain and tenderness still impact patients’ quality of life. While pro-inflammatory mediators can induce neuronal hyperactivity in the joint, the effect of anti- inflammatory mediators released from cells like regulatory T cells on sensory neurons has not been sufficiently investigated. This PhD project will investigate direct and indirect interactions between sensory neurons and regulatory T cells/ other T cell subsets in the joint in IA. An in-silico ligand-receptor interaction analysis will be matched with in vitro approaches verifying the identified interactions using synovial fluid T cell subsets and iPSC derived sensory neurons. Next, potential modulation of identified interactions by IA therapeutics will be analysed. In addition, iPSC derived neurons will be grown through microfluidic chambers, separating cell body and nerve endings to mimic the conditions in vivo. An IA mouse model will be used to ensure translatability of the findings. We anticipate identifying ligand- receptor interactions between different T cell subsets and sensory neurons. Information on how these interactions affect nociception will help reveal new potential therapeutic targets to tackle pain in IA.