Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ

Innate lymphoid cells (ILCs) have emerged as largely tissue-resident archetypal cells of the immune system. We tested the hypotheses that renal ischemia-reperfusion injury (IRI) is a contributing factor to polarization of ILCs and that glucocorticoid-induced leucine zipper (GILZ) and cannabidiol reg...

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Main Authors: Babak Baban, Hesam Khodadadi, Kumar Vaibhav, Cristina Marchetti, Carlo Riccardi, Mahmood S. Mozaffari
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/6056373
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author Babak Baban
Hesam Khodadadi
Kumar Vaibhav
Cristina Marchetti
Carlo Riccardi
Mahmood S. Mozaffari
author_facet Babak Baban
Hesam Khodadadi
Kumar Vaibhav
Cristina Marchetti
Carlo Riccardi
Mahmood S. Mozaffari
author_sort Babak Baban
collection DOAJ
description Innate lymphoid cells (ILCs) have emerged as largely tissue-resident archetypal cells of the immune system. We tested the hypotheses that renal ischemia-reperfusion injury (IRI) is a contributing factor to polarization of ILCs and that glucocorticoid-induced leucine zipper (GILZ) and cannabidiol regulate them in this condition. Mice subjected to unilateral renal IRI were treated with the following agents before restoration of renal blood flow: cannabidiol, DMSO, transactivator of transcription- (TAT-) GILZ, or the TAT peptide. Thereafter, kidney cells were prepared for flow cytometry analyses. Sham kidneys treated with either cannabidiol or TAT-GILZ displayed similar frequencies of each subset of ILCs compared to DMSO or TAT, respectively. Renal IRI increased ILC1s and ILC3s but reduced ILC2s compared to the sham group. Cannabidiol or TAT-GILZ treatment of IRI kidneys reversed this pattern as evidenced by reduced ILC1s and ILC3s but increased ILC2s compared to their DMSO- or TAT-treated counterparts. While TAT-GILZ treatment did not significantly affect cells positive for cannabinoid receptors subtype 2 (CB2+), cannabidiol treatment increased frequency of both CB2+ and GILZ-positive (GILZ+) cells of IRI kidneys. Subsequent studies showed that IRI reduced GILZ+ subsets of ILCs, an effect less marked for ILC2s. Treatment with cannabidiol increased frequencies of each subset of GILZ+ ILCs, but the effect was more marked for ILC2s. Indeed, cannabidiol treatment increased CB2+ GILZ+ ILC2s. Collectively, the results indicate that both cannabidiol and GILZ regulate ILC frequency and phenotype, in acute kidney injury, and that the effects of cannabidiol likely relate to modulation of endogenous GILZ.
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spelling doaj-art-2a0dfa11f1384cffaff386ccfe2818f72025-02-03T05:49:31ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/60563736056373Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZBabak Baban0Hesam Khodadadi1Kumar Vaibhav2Cristina Marchetti3Carlo Riccardi4Mahmood S. Mozaffari5Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, 30912-1128, GeorgiaDepartment of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, 30912-1128, GeorgiaDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, 30912-1128, GeorgiaDepartment of Medicine, University of Perugia, ItalyDepartment of Medicine, University of Perugia, ItalyDepartment of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, 30912-1128, GeorgiaInnate lymphoid cells (ILCs) have emerged as largely tissue-resident archetypal cells of the immune system. We tested the hypotheses that renal ischemia-reperfusion injury (IRI) is a contributing factor to polarization of ILCs and that glucocorticoid-induced leucine zipper (GILZ) and cannabidiol regulate them in this condition. Mice subjected to unilateral renal IRI were treated with the following agents before restoration of renal blood flow: cannabidiol, DMSO, transactivator of transcription- (TAT-) GILZ, or the TAT peptide. Thereafter, kidney cells were prepared for flow cytometry analyses. Sham kidneys treated with either cannabidiol or TAT-GILZ displayed similar frequencies of each subset of ILCs compared to DMSO or TAT, respectively. Renal IRI increased ILC1s and ILC3s but reduced ILC2s compared to the sham group. Cannabidiol or TAT-GILZ treatment of IRI kidneys reversed this pattern as evidenced by reduced ILC1s and ILC3s but increased ILC2s compared to their DMSO- or TAT-treated counterparts. While TAT-GILZ treatment did not significantly affect cells positive for cannabinoid receptors subtype 2 (CB2+), cannabidiol treatment increased frequency of both CB2+ and GILZ-positive (GILZ+) cells of IRI kidneys. Subsequent studies showed that IRI reduced GILZ+ subsets of ILCs, an effect less marked for ILC2s. Treatment with cannabidiol increased frequencies of each subset of GILZ+ ILCs, but the effect was more marked for ILC2s. Indeed, cannabidiol treatment increased CB2+ GILZ+ ILC2s. Collectively, the results indicate that both cannabidiol and GILZ regulate ILC frequency and phenotype, in acute kidney injury, and that the effects of cannabidiol likely relate to modulation of endogenous GILZ.http://dx.doi.org/10.1155/2020/6056373
spellingShingle Babak Baban
Hesam Khodadadi
Kumar Vaibhav
Cristina Marchetti
Carlo Riccardi
Mahmood S. Mozaffari
Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
Journal of Immunology Research
title Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
title_full Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
title_fullStr Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
title_full_unstemmed Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
title_short Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ
title_sort regulation of innate lymphoid cells in acute kidney injury crosstalk between cannabidiol and gilz
url http://dx.doi.org/10.1155/2020/6056373
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