Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury.
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.
Pubmed ID: 30712871
Research resources used in this publication
- C57BL/6-Gt(ROSA)26Sortm1(HBEGF)Awai/J (RRID:IMSR_JAX:007900) (organism)
- B6.129-Trpv1tm1(cre)Bbm/J (RRID:IMSR_JAX:017769) (organism)
- B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (RRID:IMSR_JAX:006148) (organism)
- Ncr1tm1.1(icre)Viv/Ncr1+ (RRID:MGI:5308422) (organism)
- B6.129-Trpv1tm1(cre)Bbm/J (RRID:IMSR_JAX:017769) (organism)
- Ncr1tm1.1(icre)Viv/Ncr1+ (RRID:MGI:5308422) (organism)
- B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (RRID:IMSR_JAX:006148) (organism)
- IgG (H&L) Anti-Mouse, HRP (1 mg) (RRID:AB_2636911) (antibody)
- goat anti-rabbit IgG-HRP (RRID:AB_631746) (antibody)
- donkey anti-goat IgG-HRP (RRID:AB_631728) (antibody)
- Anti-Chicken IgG (H+L), made in goat (RRID:AB_2336114) (antibody)
- Alexa Fluor 488-AffiniPure Donkey Anti-Goat IgG (H+L) (RRID:AB_2340428) (antibody)
- Goat Anti-Chicken IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_142924) (antibody)
- Goat Anti-Mouse Rae-1 gamma Polyclonal antibody, Unconjugated (RRID:AB_2238016) (antibody)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2536183) (antibody)
- STMN2 Antibody (RRID:AB_10011569) (antibody)
- Anti-β-Actin Antibody (RRID:AB_476744) (antibody)
- Anti-NeuN (RRID:AB_11205760) (antibody)
- Anti-beta-Tubulin III antibody produced in rabbit (RRID:AB_262133) (antibody)
- Rabbit Anti-N-cadherin, C Terminus Monoclonal Antibody, Unconjugated, Clone EPR1792Y (RRID:AB_1977064) (antibody)
- Rat IgG2a kappa Isotype Control (eBR2a), PE, eBioscience (RRID:AB_470052) (antibody)
- Anti-GFP antibody (RRID:AB_300798) (antibody)
- Goat Anti-Mouse Nkp46 / ncr1 Polyclonal antibody, Unconjugated (RRID:AB_355192) (antibody)
- Mouse IgG1, kappa Isotype Control, Phycoerythrin Conjugated, Clone MOPC-21 (RRID:AB_395506) (antibody)
- PE anti-mouse CD314 (NKG2D) (RRID:AB_1227713) (antibody)
- CD8a Monoclonal Antibody (53-6.7), APC, eBioscience (RRID:AB_469335) (antibody)
- CD4 Monoclonal Antibody (GK1.5), PE, eBioscience (RRID:AB_465507) (antibody)
- CD3e Monoclonal Antibody (145-2C11), FITC, eBioscience (RRID:AB_464881) (antibody)
- CD45 Monoclonal Antibody (30-F11), APC, eBioscience (RRID:AB_469393) (antibody)
- CD49b (Integrin alpha 2) Monoclonal Antibody (DX5), APC, eBioscience (RRID:AB_469484) (antibody)
- CD335 (NKp46) Monoclonal Antibody (29A1.4), PE, eBioscience (RRID:AB_1210743) (antibody)
- Rat Anti-CD16 / CD32 Monoclonal Antibody, Unconjugated, Clone 2.4G2 (RRID:AB_394657) (antibody)
- InVivoMab anti-mouse IL-2 (RRID:AB_1107705) (antibody)
- LEAF Purified Rat IgG1, kappa isotype Ctrl (RRID:AB_326520) (antibody)
- LEAF(TM) Purified anti-mouse CD314 (NKG2D) (RRID:AB_1227715) (antibody)
- LEAF™ Purified anti-mouse NK-1.1 (RRID:AB_313399) (antibody)
- InVivoPlus rat IgG2a isotype control (RRID:AB_1107769) (antibody)
Additional research tools detected in this publication
Antibodies used in this publication
- Granzyme B Monoclonal Antibody (NGZB), PE, eBioscience (RRID:AB_10853811)
- goat anti-rabbit IgG-HRP (RRID:AB_631746)
- Goat Anti-Chicken IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_142924)
- donkey anti-goat IgG-HRP (RRID:AB_631728)
- Anti-Chicken IgG (H+L), made in goat (RRID:AB_2336114)
- Alexa Fluor 488-AffiniPure Donkey Anti-Goat IgG (H+L) (RRID:AB_2340428)
- IgG (H&L) Anti-Mouse, HRP (1 mg) (RRID:AB_2636911)
- Rabbit Anti-N-cadherin, C Terminus Monoclonal Antibody, Unconjugated, Clone EPR1792Y (RRID:AB_1977064)
- Anti-β-Actin Antibody (RRID:AB_476744)
- Goat Anti-Mouse Rae-1 gamma Polyclonal antibody, Unconjugated (RRID:AB_2238016)
- STMN2 Antibody (RRID:AB_10011569)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2536183)
- Anti-beta-Tubulin III antibody produced in rabbit (RRID:AB_262133)
- Goat Anti-Mouse Nkp46 / ncr1 Polyclonal antibody, Unconjugated (RRID:AB_355192)
- Anti-GFP antibody (RRID:AB_300798)
- Mouse IgG1, kappa Isotype Control, Phycoerythrin Conjugated, Clone MOPC-21 (RRID:AB_395506)
- Anti-NeuN (RRID:AB_11205760)
- CD8a Monoclonal Antibody (53-6.7), APC, eBioscience (RRID:AB_469335)
- CD4 Monoclonal Antibody (GK1.5), PE, eBioscience (RRID:AB_465507)
- Rat IgG2a kappa Isotype Control (eBR2a), PE, eBioscience (RRID:AB_470052)
- CD45 Monoclonal Antibody (30-F11), APC, eBioscience (RRID:AB_469393)
- PE anti-mouse CD314 (NKG2D) (RRID:AB_1227713)
- CD49b (Integrin alpha 2) Monoclonal Antibody (DX5), APC, eBioscience (RRID:AB_469484)
- LEAF Purified Rat IgG1, kappa isotype Ctrl (RRID:AB_326520)
- CD335 (NKp46) Monoclonal Antibody (29A1.4), PE, eBioscience (RRID:AB_1210743)
- LEAF(TM) Purified anti-mouse CD314 (NKG2D) (RRID:AB_1227715)
- Rat Anti-CD16 / CD32 Monoclonal Antibody, Unconjugated, Clone 2.4G2 (RRID:AB_394657)
- CD3e Monoclonal Antibody (145-2C11), FITC, eBioscience (RRID:AB_464881)
- InVivoPlus rat IgG2a isotype control (RRID:AB_1107769)
- InVivoMab anti-mouse IL-2 (RRID:AB_1107705)
- LEAF™ Purified anti-mouse NK-1.1 (RRID:AB_313399)
- LEAF(TM) Purified Mouse IgG2a, kappa isotype Ctrl (RRID:AB_2861018)
Associated grants
- Agency: NINDS NIH HHS, United States
Id: R01 NS074430 - Agency: Medical Research Council, United Kingdom
Id: MR/P008399/1
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
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