Victorino, Francisco and Sojka, Dorothy K. and Brodsky, Kelley S. and McNamee, Eóin N. and Masterson, Joanne C. and Homann, Dirk and Yokoyama, Wayne M. and Eltzschig, Holger K. and Clambey, Eric T. (2015) Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti-Asialo-GM1 Antibody. Journal of Immunology, 195 (10). pp. 4973-4985. ISSN 0022-1767

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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 asialoGM1 (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.

Item Type:	Article
Keywords:	Tissue-Resident; NK Cells; Mediate Ischemic Kidney Injury; Are Not Depleted; Anti-Asialo-GM1 Antibody;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12482
Identification Number:	https://doi.org/10.4049/jimmunol.1500651
Depositing User:	Joanne Masterson
Date Deposited:	26 Feb 2020 16:42
Journal or Publication Title:	Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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