@article{d3b4c507d0484c8aa5f2bdcafba428b3,
title = "Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury",
abstract = "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 = "Wallerian degeneration, autoimmunity, dorsal root ganglia, innate immunity, natural cytotoxicity, neurodegeneration, neuroimmune, neuropathic pain, peripheral neuropathy, sciatic nerve crush",
author = "Davies, {Alexander J.} and Kim, {Hyoung Woo} and Rafael Gonzalez-Cano and Jahyang Choi and Back, {Seung Keun} and Roh, {Seung Eon} and Errin Johnson and Melanie Gabriac and Kim, {Mi Sun} and Jaehee Lee and Lee, {Jeong Eun} and Kim, {Yun Sook} and Bae, {Yong Chul} and Kim, {Sang Jeong} and Lee, {Kyung Mi} and Na, {Heung Sik} and Priscilla Riva and Alban Latremoliere and Simon Rinaldi and Sophie Ugolini and Michael Costigan and Oh, {Seog Bae}",
note = "Funding Information: We thank Daniel Bullock, Yildirim Han Ozdemir, Jina Won, and Nadia Yessaad for technical assistance and Dr. Steve West for help with ImageJ macro programming. We also thank Dr. Eric Vivier and Dr. Lewis Lanier for generously providing the Ncr1icre and Rosa26raet1e mice, respectively, Dr. Noo Li Jeon and Dr. Sang Cheol Kim for the kind gift of microfluidic chambers, and Dr. David Bennett and Teodora Trendafilova for assistance with in situ hybridization. We are especially grateful to Dr. Susan E. Lewis for editing the manuscript. Finally, thank you to all the staff at the Seoul National University Dental Research Institute core facilities for their support. This work was supported by the Korean Government MEST Basic Science Research Program (NRF-2012R1A1A2040338 to A.J.D.) and by National Research Foundation of Korea grants (NRF-2016M3A9B6021209, NRF-2017M3C7A1025602, and NRF-2018R1A5A2024418 to S.B.O. and NRF-2017R1A2B3004828 to K.-M.L.). M.C. was supported by NIH grant NS074430. S.R. is supported by an MRC Clinician Scientist Fellowship (MR/P008399/1). R.G.-C. was supported by Alfonso Martin Escudero Fellowship. The laboratory of S.U. received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, under grant agreement no. 648768 from the Agence Nationnale de la Recherche (ANR; no. ANR-14-CE14-0009-01), and from the ARC foundation (no. PGA120140200817) and is supported by institutional grants from INSERM, CNRS, and Aix-Marseille University to the CIML. Funding Information: We thank Daniel Bullock, Yildirim Han Ozdemir, Jina Won, and Nadia Yessaad for technical assistance and Dr. Steve West for help with ImageJ macro programming. We also thank Dr. Eric Vivier and Dr. Lewis Lanier for generously providing the Ncr1 icre and Rosa26 raet1e mice, respectively, Dr. Noo Li Jeon and Dr. Sang Cheol Kim for the kind gift of microfluidic chambers, and Dr. David Bennett and Teodora Trendafilova for assistance with in situ hybridization. We are especially grateful to Dr. Susan E. Lewis for editing the manuscript. Finally, thank you to all the staff at the Seoul National University Dental Research Institute core facilities for their support. This work was supported by the Korean Government MEST Basic Science Research Program ( NRF-2012R1A1A2040338 to A.J.D.) and by National Research Foundation of Korea grants ( NRF-2016M3A9B6021209 , NRF-2017M3C7A1025602 , and NRF-2018R1A5A2024418 to S.B.O. and NRF-2017R1A2B3004828 to K.-M.L.). M.C. was supported by NIH grant NS074430 . S.R. is supported by an MRC Clinician Scientist Fellowship ( MR/P008399/1 ). R.G.-C. was supported by Alfonso Martin Escudero Fellowship . The laboratory of S.U. received funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation program , under grant agreement no. 648768 from the Agence Nationnale de la Recherche (ANR; no. ANR-14-CE14-0009-01 ), and from the ARC foundation (no. PGA120140200817 ) and is supported by institutional grants from INSERM , CNRS , and Aix-Marseille University to the CIML . Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = feb,
day = "7",
doi = "10.1016/j.cell.2018.12.022",
language = "English",
volume = "176",
pages = "716--728.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}