B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement

JCI Insight
Alfred Hj KimAndrey S Shaw

Abstract

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role in B cells in human disease than previously recognized. In some of these diseases, such as the minimal change disease subtype of nephrotic syndrome, pathogenic antibodies and immune complexes are not involved. We hypothesized that B cells, activated in the kidney, might produce cytokines capable of directly inducing cell injury and proteinuria. To directly test our hypothesis, we targeted a model antigen to the kidney glomerulus and showed that transfer of antigen-specific B cells could induce glomerular injury and proteinuria. This effect was mediated by IL-4, as transfer of IL-4-deficient B cells did not induce proteinuria. Overexpression of IL-4 in mice was sufficient to induce kidney injury and proteinuria and could be attenuated by JAK kinase inhibitors. Since IL-4 is a specific activator of STAT6, we analyzed kidney biopsies and demonstrated STAT6 activation in up to 1 of 3 of minimal change disease patients, suggesting IL-4 or IL-13 exposure in these patients. These data suggest that the role of B cells in nephrotic syndrome could be mediated by cytokines.

References

Nov 1, 1991·Science·R KühnW Müller
Apr 1, 1994·Clinical and Experimental Immunology·K N LaiP K Li
May 1, 1994·Clinical and Experimental Immunology·V ScivittaroF P Schena
Jan 20, 1997·The Journal of Experimental Medicine·K J ErbK Rivett
Apr 15, 1997·The Journal of Clinical Investigation·S L PengJ Craft
Nov 14, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·E OhnishiT Sairenji
Feb 7, 1998·Science·A Hall
Feb 7, 1998·Kidney International·A R KitchingS R Holdsworth
Apr 14, 1999·Kidney International·H T CookC D Pusey
Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
Sep 1, 1999·International Journal of Experimental Pathology·B M RügerP F Davis
Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D C KluthA J Rees
Aug 28, 2001·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·I EbiharaA Koyama
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bengt Johansson-Lindbom, Carl A K Borrebaeck
Sep 24, 2002·Nature Immunology·Simon FillatreauStephen M Anderton
Nov 5, 2002·Nature Reviews. Immunology·Michael D CahalanMark J Miller
Sep 4, 2003·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Peter W Mathieson
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin E DuddyAmit Bar-Or
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·David P HarrisFrances E Lund
Mar 10, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Carlos E ArayaEduardo H Garin
Mar 23, 2006·Annual Review of Immunology·Flavius Martin, Andrew C Chan
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica L TeelingJan G J van de Winkel
Apr 13, 2007·Journal of the American Society of Nephrology : JASN·Kin-Wai LaiHui-Kim Yap
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qian LiuWilliam C Gause

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Citations

Jul 31, 2020·Expert Opinion on Emerging Drugs·Howard Trachtman
Sep 30, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Manuela ColucciMarina Vivarelli
Aug 8, 2018·Frontiers in Endocrinology·Mark A Lal, Jaakko Patrakka
Nov 18, 2018·Nature Reviews. Nephrology·Kristine OleinikaAlan D Salama
Sep 27, 2018·Der Internist·J FloegeM J Moeller
Nov 27, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Julie OniszczukVincent Audard
Jan 6, 2021·CEN Case Reports·Yuki ChibaMariko Miyazaki
Oct 30, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Claire DossierGeorges Deschênes
Dec 18, 2020·Frontiers in Medicine·Manuel Alfredo Podestà, Claudio Ponticelli
Apr 29, 2021·Cell and Tissue Research·Fabian BraunTobias B Huber
Jul 3, 2021·Journal of Clinical Medicine·Janina Müller-DeileLena Schiffer
Aug 13, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Ben C ReynoldsColin C Geddes
Sep 25, 2021·Nature Reviews. Nephrology·A Richard Kitching, Michael J Hickey
Nov 19, 2021·Molecular and Cellular Pediatrics·Agnes HacklLutz Thorsten Weber

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Methods Mentioned

BETA
GTPase
transgenic
ELISA
light microscopy
scanning electron microscopy
biopsy
biopsies
transfection
FACS
transmission electron microscopy

Software Mentioned

FlowJo
ImageWarp
ImageJ

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