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The lymphotoxin β receptor is a potential therapeutic target in renal inflammation.

  • Seleznik G Division of Visceral & Transplantation Surgery, Swiss Hepato-Pancreato-Biliary Center, Zurich, Switzerland; Division of Nephrology, University Hospital, Zurich, Switzerland.
  • Seeger H Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Bauer J Institute of Virology, Technische Universität München, Helmholz Zentrum, Munich, Germany.
  • Fu K Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Czerkowicz J Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Papandile A Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Poreci U Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Rabah D Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Ranger A Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA.
  • Cohen CD Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Lindenmeyer M Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Chen J Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Edenhofer I Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Anders HJ Division of Nephrology, Medizinische Klinik und Poliklinik IV, Campus Innenstadt, University of Munich-LMU, Munich, Germany.
  • Lech M Division of Nephrology, Medizinische Klinik und Poliklinik IV, Campus Innenstadt, University of Munich-LMU, Munich, Germany.
  • Wüthrich RP Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
  • Ruddle NH Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, Connecticut, USA.
  • Moeller MJ Department of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) University Hospital Aachen, Aachen, Germany.
  • Kozakowski N Clinical Institute of Pathology, University of Vienna, Vienna, Austria.
  • Regele H Clinical Institute of Pathology, University of Vienna, Vienna, Austria.
  • Browning JL Department of Immunobiology, Biogen, Cambridge, Massachusetts, USA; Department of Microbiology and Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Heikenwalder M Institute of Virology, Technische Universität München, Helmholz Zentrum, Munich, Germany; Institute of Surgical Pathology, University Hospital, Zurich, Switzerland.
  • Segerer S Division of Nephrology, University Hospital, Zurich, Switzerland; Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. Electronic address: Stephan.segerer@usz.ch.
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  • 2015-09-24
Published in:
  • Kidney international. - 2016
chemokine
cytokine
glomerulonephritis
lupus
Adult
Animals
Cell Line
Chemokines
Disease Models, Animal
Epithelial Cells
Female
Glomerulonephritis, IGA
Humans
Immunoglobulins
Kidney Glomerulus
Kidney Tubules
Ligands
Lupus Nephritis
Lymphocytes
Lymphotoxin beta Receptor
Lymphotoxin-alpha
Lymphotoxin-beta
Male
Mesangial Cells
Mice
Middle Aged
RNA, Messenger
Signal Transduction
Transcriptome
English Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/263381
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