Autoinflammation by endogenous DNA.

In various mammalian developmental processes such as programmed cell death, erythropoiesis, and lens-cell differentiation, chromosomal DNA is degraded into nucleotides by a set of specific nucleases. If this process does not proceed smoothly, the undigested DNA causes various problems. For example, when chromosomal DNA is not degraded in the lens cells, cataracts form. In other cases, undigested DNA in macrophages activates the innate immune system, like a DNA virus, and causes strong inflammation, resulting in anemia, arthritis, and lymphopenia. Here, we discuss when, where, and how DNA is degraded to maintain mammalian homeostasis.