IL-22 sustains epithelial integrity in progressive kidney remodeling and fibrosis

Physiological Reports
Marc WeidenbuschHans-Joachim Anders

Abstract

IL-22, a member of the IL-10 cytokine family, accelerates tubule regeneration upon acute kidney injury, hence we speculated on a protective role also in chronic kidney disease. We quantified intrarenal IL-22 expression after unilateral ureteral (UUO) in wild-type mice and performed UUO in IL-22 knock-out animals. Obstruction phenotypic differences between IL22+/+ and IL22-/- mice were assessed by histology, immunohistochemistry, immunofluorescence as well as western blotting and reverse-transcriptase quantitative PCR ex vivo. Additionally, we performed in vitro experiments using both murine and human tubular cells to characterize IL-22 effects in epithelial healing. We found increasing IL-22 positivity in infiltrating immune cells over time upon UUO in wild-type mice. UUO in IL22-/- mice caused more tubular cell injury as defined by TUNEL positive cells and loss of tetragonolobus lectin staining. Instead, tubular dilation, loss of CD31+ perivascular capillaries, and interstitial fibrosis were independent of the Il22 genotype as assessed by standard histology, immunostaining, and mRNA expression profiling. In vitro experiments showed that recombinant human IL-22 significantly enhanced human tubular epithelial cell proliferation ...Continue Reading

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Citations

Jan 10, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Takamasa IwakuraHans Joachim Anders
Jan 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bernard C LoKelly M McNagny
May 23, 2019·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Laurence M BlackAnupam Agarwal
Oct 11, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Takamasa IwakuraHans-Joachim Anders
Jun 12, 2020·Clinical & Translational Immunology·Molly A Ingersoll, Malcolm R Starkey
May 7, 2020·Nature Reviews. Nephrology·Christian KurtsUlf Panzer
Aug 8, 2021·Cells·Beatriz Delgado-ValeroErnesto Martínez-Martínez
Oct 2, 2021·PloS One·Sharven TaghaviJay Kolls

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