title: Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti-Asialo-GM1 Antibody.
abstract: NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. Whereas conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. In the present study, we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions. Kidney trNK cells developed independent of NFIL3 and T-bet, and they expressed a distinct cell surface phenotype as compared with cNK cells. Among these, trNK cells had reduced asialo-GM1 (AsGM1) expression relative to cNK cells, a phenotype observed in trNK cells across multiple organs and mouse strains. Strikingly, anti-AsGM1 Ab treatment, commonly used as an NK cell-depleting regimen, resulted in a robust and selective depletion of cNKs, leaving trNKs largely intact. Using this differential depletion, we tested the relative contribution of cNK and trNK cells in ischemic kidney injury. Whereas anti-NK1.1 Ab effectively depleted both trNK and cNK cells and protected against ischemic/reperfusion injury, anti-AsGM1 Ab preferentially depleted cNK cells and failed to protect against injury. These data demonstrate unanticipated specificity of anti-AsGM1 Ab depletion on NK cell subsets and reveal a new approach to study the contributions of cNK and trNK cells in vivo. In total, these data demonstrate that trNK cells play a key role in modulating local responses to ischemic tissue injury in the kidney and potentially other organs.
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045; Immunology Graduate Program, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Francisco
authors.identifier: http://orcid.org/0000-0001-7626-3219
authors.initials: F
authors.lastname: Victorino
authors.affiliation: Rheumatology Division, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Sojka
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Kelley S
authors.identifier: http://orcid.org/0000-0003-0732-7703
authors.initials: KS
authors.lastname: Brodsky
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Eoin N
authors.identifier: http://orcid.org/0000-0002-3331-3148
authors.initials: EN
authors.lastname: McNamee
authors.affiliation: Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045; Digestive Health Institute, Children's Hospital Colorado, Aurora, CO 80045; and.
authors.forename: Joanne C
authors.identifier: http://orcid.org/0000-0002-8336-9879
authors.initials: JC
authors.lastname: Masterson
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Dirk
authors.initials: D
authors.lastname: Homann
authors.affiliation: Rheumatology Division, Washington University School of Medicine, St. Louis, MO 63110; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045; Eric.Clambey@ucdenver.edu.
authors.forename: Eric T
authors.identifier: http://orcid.org/0000-0002-7972-9544
authors.initials: ET
authors.lastname: Clambey
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000276:immunology*; D007511:Ischemia / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout
chemical_list: D000906:Antibodies; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside