# Erythropoietin and trained immunity intransplantation

> **NIH NIH R56** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $456,300

## Abstract

Summary
Transplantation
T
critical Macrophages are constantly exposed to damage- and pathogen-associated
molecular patterns (DAMPs and PAMPs). These stimuli directly induce the release of proinflammatory
molecules, but they also promote epigenetic and metabolic modifications, leading to a long-lasting increase in
macrophage functional responsiveness (trained immunity). The identification of therapies to target trained
immunity is an unmet need in transplant medicine.
is the ideal treatment f or end-stage organ failure, but long-term graft survival is still insufficient.
and B cells have a key role in acute rejection, but recent evidence indicates that also innate immune cells are
 in alloimmune response.
This
erythropoietin
 grant renewal builds logically on the results generated during the first funding cycle showing that
(EPO)has immunomodulating activity in murine and human cells. We showed that EPO promotes
conversion of naïve T cells into regulatory T cells (Treg) in mice and humans, leading to prolonged graft survival
and reduced severity of multiple autoimmune disease models in mice. Our new preliminary data indicate that
EPO has also inhibitory effects on macrophage training and hinders the proinflammatory program of previously
trained cells. This effect, that occurs through a direct interaction with the EPO receptor on myeloid cells, leads
to prolonged graft survival in mice that underwent training. The present proposal will address the mechanisms
responsible for these effects using in vivo and in vitro systems. We will also test the role of endogenous EPO on
trained immunity.
The results of this research project will provide new insight on the role of macrophage training in alloimmune
responses and how EPO counteracts them. The data have the potential to unravel cellular and molecular
pathways that are important in the pathophysiology of rejection and to identify new therapeutic targets. The fact
that EPO is FDA-approved, makes our findings easier to be translated into the clinic.

## Key facts

- **NIH application ID:** 11133563
- **Project number:** 2R56AI132949-06
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Paolo Cravedi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $456,300
- **Award type:** 2
- **Project period:** 2018-02-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11133563

## Citation

> US National Institutes of Health, RePORTER application 11133563, Erythropoietin and trained immunity intransplantation (2R56AI132949-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11133563. Licensed CC0.

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