Immune regulation by erythroid cells: how erythroid progenitor cells and mature red blood cells shape immunity

Once considered to be passive oxygen carriers, erythroid cells are now recognized as dynamic modulators of immune responses. Erythroid progenitors and precursors, collectively known as CD71⁺ erythroid cells, can suppress innate and adaptive immune responses in neonates, in mothers during pregnancy, in chronic conditions such as cancer and autoimmunity, and during infection with viruses, including SARS-CoV-2 and HIV. Mature red blood cells engage pathogens directly, scavenge chemokines, cytokines and nucleic acids, and modulate immune functions through redox buffering and receptor-mediated interactions. The immune effects of red blood cells are highly context dependent, ranging from suppression to activation. This Review highlights the emerging field of erythroid-immune crosstalk and its translational potential in the settings of infection, cancer, pregnancy and chronic inflammatory conditions.