Potent but transient immunosuppression of T-cells is a general feature of CD71⁺erythroid cells

Abstract

Erythroid progenitor cells (EPCs) have been recently recognized as potent immunoregulatory cells with defined roles in fetomaternal tolerance and immune response to infectious agents in neonates and cancer patients. Here, we show that early-stage EPCs are enriched in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). EPCs expansion in anemic mice leads to the L-arginine depletion in the spleen microenvironment resulting in the suppression of T-cell responses. In humans with anemia, EPCs expand and express both ARG1 and ARG2 that participate in suppressing the proliferation and production of IFN-γ from T-cells. EPCs differentiated from peripheral blood mononuclear cells potently suppress T-cell proliferation and this effect is the most prominent for CD49dhi CD71hiEPCs. The suppressive properties disappear during erythroid differentiation as more differentiated EPCs as well as mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of EPCs in the regulation of immune response.Abstract Figure