Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors

Abstract

Apoptotic cells are recognized and subsequently engulfed by macrophages and immature dendritic cells. The engulfed dead cells are transported to the lysosomes of macrophages, and their components are degraded into amino acids and nucleotides for reuse. In mammals, macrophages also engulf nuclei expelled from erythroid precursors in the final stage of definitive erythropoiesis. Failure to swiftly engulf dead cells at the germinal centers of lymphoid organs causes systemic lupus erythematosus-type autoimmune diseases. In contrast, failure to efficiently degrade the DNA of dead cells or erythroid cell nuclei activates innate immunity, causing lethal anemia in the fetus and chronic arthritis in adults.