Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f

Benjamin Fuhrmann; Jifu Jiang; Patrick Mcleod; Xuyan Huang; Shilpa Balaji; Jaqueline Arp; Hong Diao; Shengwu Ma; Tianqing Peng; Aaron Haig; Lakshman Gunaratnam; Zhu-Xu Zhang; Anthony M. Jevnikar

Current Research in Immunology (Jan 2024)

Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f

Benjamin Fuhrmann,
Jifu Jiang,
Patrick Mcleod,
Xuyan Huang,
Shilpa Balaji,
Jaqueline Arp,
Hong Diao,
Shengwu Ma,
Tianqing Peng,
Aaron Haig,
Lakshman Gunaratnam,
Zhu-Xu Zhang,
Anthony M. Jevnikar

Affiliations

Benjamin Fuhrmann: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada
Jifu Jiang: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada
Patrick Mcleod: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada
Xuyan Huang: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada
Shilpa Balaji: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada
Jaqueline Arp: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada
Hong Diao: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada
Shengwu Ma: Department of Microbiology and Immunology, Western University, London, Ontario, Canada
Tianqing Peng: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
Aaron Haig: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
Lakshman Gunaratnam: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada
Zhu-Xu Zhang: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Corresponding author. Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada.
Anthony M. Jevnikar: Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada; Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Multi-Organ Transplantation Program, London Health Sciences Centre, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Corresponding author. Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada.

Journal volume & issue: Vol. 5
p. 100081

Abstract

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NK cells participate in ischemia reperfusion injury (IRI) and transplant rejection. Endogenous regulatory systems may exist to attenuate NK cell activation and cytotoxicity in IRI associated with kidney transplantation. A greater understanding of NK regulation will provide insights in transplant outcomes and could direct new therapeutic strategies. Kidney tubular epithelial cells (TECs) may negatively regulate NK cell activation by their surface expression of a complex family of C-type lectin-related proteins (Clrs). We have found that Clr-b and Clr-f were expressed by TECs. Clr-b was upregulated by inflammatory cytokines TNFα and IFNγ in vitro. Silencing of both Clr-b and Clr-f expression using siRNA resulted in increased NK cell killing of TECs compared to silencing of either Clr-b or Clr-f alone (p < 0.01) and when compared to control TECs (p < 0.001). NK cells treated in vitro with soluble Clr-b and Clr-f proteins reduced their capacity to kill TECs (p < 0.05). Hence, NK cell cytotoxicity can be inhibited by Clr proteins on the surface of TECs. Our study suggests a synergistic effect of Clr molecules in regulating NK cell function in renal cells and this may represent an important endogenous regulatory system to limit NK cell-mediated organ injury during inflammation.

Published in Current Research in Immunology

ISSN: 2590-2555 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine
Website: https://www.journals.elsevier.com/current-research-in-immunology

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