Overview
- Stanford-led researchers report in Nature that erythropoietin signaling programs dendritic cells to induce regulatory T cells and enforce peripheral tolerance in mice.
- After total lymphoid irradiation, dendritic cells upregulated the EPO receptor and circulating EPO levels rose, indicating a systemic cue that primes tolerance.
- Genetic deletion of the EPO receptor in dendritic cells prevented tolerance and caused rejection of mismatched bone marrow transplants, converting the cells into potent immune activators.
- In melanoma and colon cancer models, EPO receptor–expressing dendritic cells infiltrated tumors and dampened cytotoxic T cells, while receptor deletion increased antitumor T cells and shrank tumors.
- The authors propose that this pathway can be turned on to induce tolerance or turned off to boost immunity, though all findings are preclinical and build on prior work linking tumor-derived EPO to immunosuppressive macrophages.