A Critical Role for Murine Complement Regulator Crry in Fetomaternal Tolerance

TLDR

Complement is a key component of innate immunity, and its regulation protects tissues from inflammation, yet mice lacking the regulator decay‑accelerating factor remain normal. The authors generated Crry‑deficient mice to investigate the in vivo role of this complement regulator. Crry‑deficient embryos died due to complement deposition and placental inflammation, and breeding into a C3‑deficient background rescued them, demonstrating that complement regulation is essential for fetal survival at the fetomaternal interface.

Abstract

Complement is a component of natural immunity. Its regulation is needed to protect tissues from inflammation, but mice with a disrupted gene for the complement regulator decay accelerating factor were normal. Mice that were deficient in another murine complement regulator, Crry, were generated to investigate its role in vivo. Survival of Crry −/− embryos was compromised because of complement deposition and concomitant placenta inflammation. Complement activation at the fetomaternal interface caused the fetal loss because breeding to C3 −/− mice rescued Crry −/− mice from lethality. Thus, the regulation of complement is critical in fetal control of maternal processes that mediate tissue damage.