Abstract: FR-PO696

Erythropoietin (EPO) Ameliorates Lupus Nephritis by Inhibiting TFH and Increasing Treg

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Angeletti, Andrea, Icahn School of Medicine at Mount Sinai, New York, United States
  • Donadei, Chiara, Icahn School of Medicine at Mount Sinai, New York, United States
  • D'Agati, Vivette D., Columbia University College of Physicians and Surgeons, New York, New York, United States
  • Cumpelik, Arun, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Manrique, Joaquin, Complejo Hospital de Navarra, Pamplona, Spain
  • Fribourg, Miguel L, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • La Manna, Gaetano, DIMES, Bologna, Italy
  • Heeger, Peter S., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Systemic lupus erythematosus (SLE) is characterized by impaired immune regulation and enhanced follicular helper T cell (Tfh)-dependent B cell activation, autoantibody production and tissue deposition/injury. Building upon evidence that EPO inhibits effector T cells (Teff) while promoting regulatory T cells (Treg) (JASN 2017), we tested the effects of EPO in murine lupus.

Methods

We treated MRL/lpr mice with rEPO (5,000IU/ml, 3/week mo 4-6) or vehicle, serially measured proteinuria and at 6 mo quantified anti-dsDNA, glomerular Ig deposition and splenic Treg/Teff/Tfh. We also administered EPO or vehicle to (bxd)F1 mice given B6 spleen cells and quantified splenic Tfh, Treg and germinal center (GC) B cells 2 weeks later.

Results

In MRL/lpr mice, rEPO increased Treg (20.1±3.3 vs. 11.5±4.2%; P<0.05) and reduced proteinuria, autoantibodies, glomerular IgG deposition, and histological score (is that right?) (Fig 1A). In the parent to F1 model, EPO inhibited TFH and GC B cells formation (Fig 1B-C), while it increased Treg cells vs. vehicle (1.4±0.3 vs. 0.4±0.2%; P<0.05).

Conclusion

EPO administration inhibits TFH and GC B cell formation while promoting Treg, together reducing the clinical and histological expression of murine lupus nephritis. Together with our published evidence that EPO promotes human Treg, the data support safety/efficacy testing of rEPO as an immunemodulating agent in lupus patients.