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Kidney Week

Abstract: FR-PO062

Repetitive Ischemic Injuries to the Kidneys Result in Lymph Node Fibrosis and Impaired Healing

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Maarouf, Omar H., Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States
  • Uehara, Mayuko, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Kasinath, Vivek, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Solhjou, Zhabiz, University of Central Florida, Kissimmee, Florida, United States
  • Banouni, Naima M., Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Bahmani, Baharak, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Jiang, Liwei, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Yilmam, Osman Arif, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Guleria, Indira, Children's Hospital Boston, Boston, Massachusetts, United States
  • Lovitch, Scott B., Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Grogan, Jane L., Genentech, South San Francisco, California, United States
  • Sage, Peter, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Bromberg, Jonathan, University of Maryland, Baltimore, Maryland, United States
  • McGrath, Martina M., Harvard University, West Roxbury, Massachusetts, United States
  • Abdi, Reza, Brigham and Women''s Hospital, Boston, Massachusetts, United States
Background

The contribution of the kidney-draining lymph node (KLN) to the pathogenesis of ischemia-reperfusion injury (IRI) of the kidney and its subsequent recovery has not been explored in depth. In addition, the mechanism by which repetitive IRI contributes to renal fibrosis remains poorly understood.

Methods

Transgenic mice were used. Ischemia Reperfusion Injury (IRI) surgeries on mice were performed using clamps. Aseptic techniques were used to culture cells. Protein and mRNA were extracted according to generally accepted techniques. Light and electron microscopy were used in addition to immunofluorescence staining.

Results

Herein, we have found that IRI of the kidney is associated with expansion of high endothelial venules (HEVs) and activation of fibroblastic reticular cells (FRC) in the KLN, as demonstrated by significant expansion in the extracellular matrix. The lymphotoxin α signaling pathway mediates activation of FRCs. Chronic blockade of the LTα –LTβr axis with lymphotoxin β receptor immunoglobulin (LTβr-Ig) resulted in marked alteration of the KLN as well as augmentation of renal fibrosis. In the acute setting, depletion of FRCs reduced T cell activation in the KLN and ameliorated renal injury 2 days post-IRI. Repetitive renal IRI was associated with senescence of FRCs, fibrosis of the KLN, and renal scarring. FRC administration promoted repair of the kidney and KLN

Conclusion

Our study is novel in emphasizing the critical role of FRCs in KLN in both the initiation and repair phases of injury following IRI of the kidney. We also highlight the potential of FRCs as a cellular therapy to control inflammation and promote renal repair following IRI important in the progression of renal fibrosis.

Funding

  • Other NIH Support