Podocytes use FcRn to clear IgG from the glomerular basement membrane

Shreeram Akilesh, Tobias B. Huber, Hui Wu, Gary Wang, Björn Hartleben, Jeffrey B. Kopp, Jeffrey H. Miner, Derry C. Roopenian, Emil R. Unanue, Andrey S. Shaw

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged, and tracer studies showed delayed clearance of IgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases.

Original languageEnglish
Pages (from-to)967-972
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number3
DOIs
StatePublished - Jan 22 2008

Keywords

  • Fc receptor
  • Glomerulonephritis

Fingerprint

Dive into the research topics of 'Podocytes use FcRn to clear IgG from the glomerular basement membrane'. Together they form a unique fingerprint.

Cite this