Complex regulation of the immune response is necessary to support effective defense of an organism against hostile invaders and to maintain tolerance to harmless microorganisms and autoantigens. Recent studies revealed previously unappreciated roles of CD71⁺ erythroid cells (CECs) in regulation of the immune response. CECs physiologically reside in the bone marrow where erythropoiesis takes place. Under stress conditions, CECs are enriched in some organs outside of the bone marrow as a result of extramedullary erythropoiesis. However, the role of CECs goes well beyond the production of erythrocytes. In neonates, increased numbers of CECs contribute to their vulnerability to infectious diseases. On the other side, neonatal CECs suppress activation of immune cells in response to abrupt colonization with commensal microorganisms after delivery. CECs are also enriched in the peripheral blood of pregnant women as well as in the placenta and are responsible for the regulation of feto-maternal tolerance. In patients with cancer, anemia leads to increased frequency of CECs in the peripheral blood contributing to diminished antiviral and antibacterial immunity, as well as to accelerated cancer progression. Moreover, recent studies revealed the role of CECs in HIV and SARS-CoV-2 infections. CECs use a full arsenal of mechanisms to regulate immune response. These cells suppress proinflammatory responses of myeloid cells and T-cell proliferation by the depletion of ʟ-arginine by arginase. Moreover, CECs produce reactive oxygen species to decrease T-cell proliferation. CECs also secrete cytokines, including transforming growth factor β (TGF-β), which promotes T-cell differentiation into regulatory T-cells. Here, we comprehensively describe the role of CECs in orchestrating immune response and indicate some therapeutic approaches that might be used to regulate their effector functions in the treatment of human conditions.

免疫反应的复杂调节对于支持生物体对敌对入侵者的有效防御和维持对无害微生物和自身抗原的耐受性是必要的。最近的研究揭示了 CD71 ^{+以前未被重视的作用}红细胞 (CECs) 调节免疫反应。CEC 在生理上存在于发生红细胞生成的骨髓中。在压力条件下，由于髓外红细胞生成，CEC 在骨髓外的某些器官中富集。然而，CEC 的作用远远超出了红细胞的产生。在新生儿中，CEC 数量的增加增加了他们对传染病的脆弱性。另一方面，新生儿 CEC 抑制免疫细胞的激活，以响应分娩后共生微生物的突然定植。CECs 还富含孕妇的外周血和胎盘，并负责调节母胎耐受性。在癌症患者中，贫血会导致外周血中 CEC 的频率增加，从而导致抗病毒和抗菌免疫力降低，并加速癌症进展。此外，最近的研究揭示了 CEC 在 HIV 和 SARS-CoV-2 感染中的作用。CEC 使用一整套机制来调节免疫反应。这些细胞通过精氨酸酶消耗 ʟ-精氨酸来抑制骨髓细胞的促炎反应和 T 细胞增殖。此外，CECs 产生活性氧物质以减少 T 细胞增殖。CEC 还分泌细胞因子，包括促进 T 细胞分化为调节性 T 细胞的转化生长因子 β (TGF-β)。这里，