Death and fire—the concept of necroinflammation

Death may be either immunogenic or not, and fire (inflammation) (Fig. 1 ) potentiates the cellular damage, but also initiates organ regeneration. With close to 200,000,000,000 cells dying in our bodies each day by apoptosis, it is obvious that this pathway of regulated cell death does not cause severe inflammation. However, more recently discovered necrotic type cell death pathways, such as necroptosis, ferroptosis, and pyroptosis, inevitably release intracellular damage-associated molecular patterns (DAMPs). In an organism, this leads to access of tissue-resident immune cells directly to proimmunogenic intracellular factors. Clinically important examples in which necroinflammation is involved are antinuclear antibodies (ANAs) and anti-double-stranded DNA antibodies, which drive human autoimmune diseases. Fig. 1 Tod und Feuer, Paul Klee 1940 (Zentrum Paul Klee, Bern, Switzerland , used with permission ). In 1940, the German expressionist Paul Klee painted “Tod und Feuer” (“Death and Fire”). Oil on distemper on jute. With himself passing away on June 29 of the same year, it is today considered one of his final masterpieces. Klee at this time suffered from an autoimmune disease known as scleroderma. The disease heavily affected his joints and hardly allowed painless painting. Scleroderma is associated with the development of autoantibodies, the most common ones being anti-nuclear antibodies, and represents a typical example of a degenerative disease driven by necroinflammation Full size image