This Review discusses how the study of novel mouse models of human ADAR1 deficiency has led to the identification of the innate immune receptors recognizing endogenous immunostimulatory double-stranded RNA and their respective downstream signalling pathways that induce autoinflammatory pathology.

This Review covers the biology of anti-cytokine autoantibodies and their varied roles in causing, preventing and treating diseases. Recent reports of anti-type I interferon autoantibodies in critical COVID-19 have led to renewed interest in this topic, which offers fascinating insights into the reversibility of immune tolerance and the origins of autoimmunity in otherwise healthy individuals.

Cryptosporidium are protozoan parasites that infect intestinal epithelial cells and can cause severe diarrhoeal disease, particularly in malnourished children. This Review summarizes the immune mechanisms that protect against this parasitic infection, highlighting the innate mechanisms that detect Cryptosporidium at the intestinal epithelium and the adaptive immune mechanisms that mediate resistance.

This Review provides a guide to complement and its emerging roles in processes beyond innate immune defence such as in early development, tissue immunometabolism, tissue regeneration and cancer immunity. Moreover, our improved understanding of its role in disease pathology has opened new options for complement-based therapeutics.