# Erythropoietin mediated immunoregulation in murine lupus nephritis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $423,750

## Abstract

Abstract
Systemic
characterized
production
treatment
which
lupus erythematosus (SLE) is a chronic, potentially fatal autoimmune disease
by abnormal activation of autoreactive T and B cells resulting in the
of autoantibodies that cause widespread tissue and organ damage. Current
 strategies rely heavily corticosteroids and immunosuppressive agents,
are limited by suboptimal efficacy and by a significant burden of morbidity.
,
on
Identification of alternative, safer and more comprehensive approaches targeting
different elements of disease pathogenesis need to be explored.
Our new published and preliminary data support the provocative and intriguing concept
that erythropoietin (EPO), a hormone produced predominantly by the kidney in adults,
plays an unanticipated role in controlling autoimmune response in lupus and improving
clinical outcomes. Expanding beyond EPO's established role in erythrocyte
development, our new data demonstrate that EPO a) improves disease severity in
murine models of lupus, b) inhibits mouse and human Th17, T follicular helper cells
(TFH), and Th1, while it increases T follicular regulatory cells (Tfr), c) induces and
stabilizes Treg, and d) inhibits germinal center B cell formation and autoantibody
production. We have identified molecular mechanisms that link EPO to some of these
effects and show that they apply to humans given clinically used doses of EPO. EPO
therapy, at doses used to correct anemia, augments frequencies of circulating
CD4+CD25+CD127lo Treg in human subjects. Altogether, our findings support the
following hypothesis to be tested in this project: EPO directly inhibits autoreactive
Th17 and TFH, and simultaneously induces and maintains Treg and Tfr, together
reducing disease severity in lupus.
We will test this hypothesis by determining the effects of exogenous and kidney-derived
EPO on murine lupus (aim 1), deciphering the mechanisms through which EPO
selectively inhibits Th17 and TFH (aim 2), while EPO promotes Treg/Tfr induction and
stability (aim 3). The proposed work will define the role of EPO as a mediator of self-
tolerance and will delineate cellular and molecular mechanisms underlying EPO's effects
on Th17, TFH, and Treg/Tfr. In addition to deciphering mechanisms, the studies will
provide preclinical data on the utility of EPO as a therapeutic agent for improving
disease activity in animals, findings that could potentially be translated to SLE patients.

## Key facts

- **NIH application ID:** 9851331
- **Project number:** 5R01AI132949-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Paolo Cravedi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851331

## Citation

> US National Institutes of Health, RePORTER application 9851331, Erythropoietin mediated immunoregulation in murine lupus nephritis (5R01AI132949-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851331. Licensed CC0.

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