Investigating cytotoxic neuroimmune interactions in painful nerve injury

The sensory nervous system is a target for recognition by various immune factors after painful nerve injury (Davies et al., 2020; PMID: 32153361). While we know a great deal about immune mechanisms causing pain, we are only just beginning to understand the role it plays in its resolution. We have previously shown that nerve injury upregulates the stress ligand RAET1 that signals to natural killer (NK) cells via the immune receptor NKG2D. This neuro-immune interaction results in the pruning of intact primary sensory axons within the injured nerve (Davies et al., 2019; PMID: 30712871), that are otherwise a significant risk factor in neuropathic hypersensitivity (Kim et al., 2023a; PMID: 37366595). This neuro-immune interaction raises the possibility of an immune-based therapy for the treatment of neuropathic pain (Kim et al., 2023b; PMID: 37385878).

We use a combination of cell culture and mouse models to interrogate the receptor-ligand interactions between the peripheral nerve and killer immune cells injury and disease. We work closely with clinicians to collect and analyse relevant human samples and perform translational mechanistic studies using humanised cell culture models. Students will have the opportunity to learn animal behaviour, stem cell technology, live-imaging and high-dimensional flow cytometry, among other techniques, to understand the cellular and molecular interactions involved in cytotoxic neuro-immunity and its consequences for neuronal function and pain.