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Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury
- Davies, Alexander J., Kim, Hyoung Woo, Gonzalez-Cano, Rafael, Choi, Jahyang, Back, Seung Keun, Roh, Seung Eon, Johnson, Errin, Gabriac, Melanie, Kim, Mi-Sun, Lee, Jaehee, Lee, Jeong Eun, Kim, Yun Sook, Bae, Yong Chul, Kim, Sang Jeong, Lee, Kyung-Mi, Na, Heung Sik, Riva, Priscilla, Latremoliere, Alban, Rinaldi, Simon, Ugolini, Sophie, Costigan, Michael, Oh, Seog Bae
- Cell 2019 v.176 no.4 pp. 716-728.e18
- adults, axons, cytotoxicity, hypersensitivity, ligands, natural killer cells, nerve tissue, peripheral nerves, peripheral nervous system diseases, retinoic acid, sensation, therapeutics
- Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.