Redox Modulation of Erythropoiesis by Selenoproteins

Erythroblasts are constantly challenged by oxidative stress arising from the accumulation of free heme and reactive radicals, particularly during stress erythropoiesis, which is triggered by inflammatory signals. In response to infection or tissue damage, stress erythropoiesis serves as a compensatory mechanism to overcome inhibition of steady-state erythropoiesis by pro-inflammatory cytokines to sustain abundant red blood cell (RBC) production. Maturation of erythroblasts during stress erythropoiesis critically depends on the erythroblastic island (EBI) microenvironment, composed of a central macrophage and surrounding immature progenitors. Within this niche, the dynamic balance between inflammatory and resolution pathways is essential for proper erythroblast development and adaptation under stress. Selenium (Se), an essential trace element, incorporated into selenoproteins via the 21st amino acid selenocysteine, imparts antioxidant and redox-regulatory activity, which govern erythroblast-intrinsic signaling as well as microenvironmental regulation. Depletion of the selenoproteome or selenium in the diet results in mild anemia and impaired stress erythropoiesis. However, the contributions of individual selenoproteins to erythroblast development is not well understood. Given the importance of selenoproteins in influencing macrophage polarization, its contribution to the regulation of the erythropoietic microenvironment deserves further study. In this review, we highlight the role of selenium and selenoproteins in stress erythropoiesis, emphasizing their functions in supporting erythroblast development and modulating the erythropoietic niche.