Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons

Gamage, Kanchana K.; Cheng, Irene H.; Park, Rachel E.; Karim, Mardeen S.; Edamura, Kazusa; Hughes, Christopher C.W.; Spano, Anthony; Erişir, Alev; Deppmann, Christopher D.

doi:10.1016/j.cub.2017.03.058

Cited by 2 publications

(1 citation statement)

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“…Axon degeneration is generally regarded as neuron autonomous; however, discrepancies in the timing of axon degeneration after injury ( Neukomm and Freeman, 2014 ) and recent evidence pointing to the role of as-yet-unknown extrinsic factors in axon fragmentation ( Gamage et al., 2017 ) open up the possibility of a role for immune cells with cytotoxic action in the degeneration process itself.…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury

Davies

Kim

González‐Cano

et al. 2019

Cell

109

103

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SummarySensory 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.

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Section: Introductionmentioning

confidence: 99%