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Abstract: SA-PO371

Knockout of the Neonatal Fc Receptor (FcRn) Abrogates IL6 Mediated Signaling in Podocytes

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Tonsawan, Pantipa, Khon Kaen University, Khon Kaen, Thailand
  • Dylewski, James F., University of Colorado Hospital, Aurora, Colorado, United States
  • Blaine, Judith, University of Colorado Denver, AURORA, Colorado, United States
Background

FcRn has been shown to be required for antigen presentation in dendritic cells and global knockout of FcRn attenuates immune mediated kidney disease. FcRn is expressed in podocytes but the role of podocyte FcRn in immune mediated renal disease is unknown. Previous work has shown that podocytes express the IL6 receptor and produce IL6 under proinflammatory conditions. Here we examine the role of FcRn in the IL6-mediated inflammatory response in podocytes.

Methods

We examined IL6 production by ELISA and expression by qPCR in WT and FcRn knockout (KO) podocytes after treatment with proinflammatory stimuli including albumin, IgG, interferon gamma (IFNγ) and immune complexes. We performed western blot analysis of the IL6-mediated Jak/STAT signaling pathway after treatment of WT and FcRn KO podocytes with IFNγ and immune complexes. We also examined podocyte motility in WT and FcRn KO podocytes in vitro after a proinflammatory challenge. In vivo, we examined synaptopodin expression in WT and podocyte-specific FcRn KO mice as inhibition of IL6 has been shown to decrease synaptopodin expression.

Results

We found that FcRn KO podocytes produced minimal amounts of IL6 after treatment with albumin, IgG or immune complexes whereas WT podocytes had a robust response. FcRn KO podocytes also had minimal expression of IL6 as measured by qPCR compared to WT after an immune challenge. By western blot analysis, FcRn KO podocytes expressed significantly less phosphorylated STAT3, a key component in the IL6 signaling pathway, than WT after treatment with IFNγ or immune complexes. In a scratch assay to assess mobility, FcRn KO podocytes showed increased mobility compared to WT, suggesting defects in actin dynamics. Expression of synaptopodin in the glomerulus was also significantly reduced in podocyte-specific FcRn KO mice compared to controls at 6 and 12 months of age, suggesting FcRn mediated defects in synaptopodin regulation.

Conclusion

This study shows that in podocytes, FcRn modulates the IL6-mediated response to proinflammatory stimuli and regulates podocyte motility and synaptopodin expression.

Funding

  • NIDDK Support