*Purpose: Building upon our previously generated evidence that erythropoietin (EPO) directly inhibits effector T cells (JASN 2015, 2017) and reduces autoantibody formation in murine lupus, we hypothesized that EPO affects also T follicular helper cells (T_FH) function.

*Methods: We administered EPO or vehicle to (bxd)F1 mice given B6 T cells and quantified splenic T_FH and germinal center (GC) B cells 2 weeks later. While this graft-versus-host-disease (GVHD) model allows to study alloreactive T_FH cells, it is not associated with a clinical phenotype. Therefore, we next treated (dxb/d)F1 mice given DBA/2J spleen cells with EPO or vehicle and quantified anti-dsDNA IgG, proteinuria, renal histology, T_FH and GC cells at 6 weeks thereafter. In vitro experiments tested the effect of EPO on B cells stimulated with anti-IgM, anti-CD40 or LPS.

*Results: In the (bxd) parent to F1 model, EPO inhibited T_FH and GC B cells formation (Fig 1A). Also in the (dxb/d) parent to F1 model, EPO-induced inhibition of T_FH (-20.6±3.5%; p<0.01) and GC B cells (-3.6±0.8%; p<0.001) and this was associated with reduced autoantibodies, proteinuria and renal histological changes (Figure 1B-D). In vitro, EPO did not affect IgG class switch rate of stimulated B cells.

*Conclusions: EPO administration inhibits T_FH and GC B cell formation, together reducing the clinical and histological expression of murine lupus nephritis in parent-to-F1 models. Together with our published evidence that EPO promotes human Treg, the data support safety/efficacy testing of rEPO as an immunemodulating agent in to inhibit T_FH and alloantibody formation.

Figure 1: Percentages of splenic H2kD^–CD4⁺PD1⁺CXCR5⁺ T_FH and B220⁺GL7⁺Fas⁺ GC B cells in (bxd)F1 mice injected with B6 T cells 2 weeks prior and treated with vehicle or EPO (A). Representative renal histology (B), urinary albumin/creatinine (C), and anti-dsDNA IgG (D) in (dxb/d)F1 recipients of DBA/2J spleen cells and treated with vehicle or EPO for 6 weeks.

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