Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury

Alexander J Davies (1) , Hyoung Woo Kim (1) , Rafael Gonzalez-Cano (2) , Jahyang Choi (1) , Seung Keun Back (1) , Seung Eon Roh (1) , Errin E. Johnson (3) , Mélanie Gabriac (4) , Mi-Sun Kim (1) , Jaehee Lee (1) , Jeong Eun Lee (5) , Yun Sook Kim (6) , Yong Chul Bae (6) , Sang Jeong Kim (1) , Kyung-Mi Lee (5) , Heung Sik Na (5) , Priscilla Riva (2) , Alban Latremoliere (7) , Simon Rinaldi (8) , Sophie Ugolini (4) , Michael Costigan (2) , Seog Bae Oh (1)

1 SNU - Seoul National University [Seoul]
2 HMS - Harvard Medical School [Boston]
3 Sir William Dunn School of Pathology [Oxford]
4 CIML - Centre d'Immunologie de Marseille - Luminy
5 Korea University [Seoul]
6 KNU - Kyungpook National University [Daegu]
7 Johns Hopkins University School of Medicine [Baltimore]
8 Nuffield Department of Clinical Neurosciences [Oxford]

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.

Keywords: autoimmunity; dorsal root ganglia; innate immunity; natural cytotoxicity; neurodegeneration; neuroimmune; neuropathic pain; peripheral neuropathy; sciatic nerve crush; Wallerian degeneration

Domains: Life Sciences [q-bio]; Immunology

Alexander J Davies, Hyoung Woo Kim, Rafael Gonzalez-Cano, Jahyang Choi, Seung Keun Back, et al.. Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury. Cell, 2019, 176 (4), pp.716-728.e18. ⟨10.1016/j.cell.2018.12.022⟩. ⟨hal-02346154⟩