Behind Science of WARS 1

Tryptophanyl-tRNA synthetase (WARS1) is an essential protein for cell survival as an enzyme that links tryptophan to the corresponding tRNA during protein synthesis. Human WARS1 acquired new functions in the immune system during the evolutionary process (Nat Microbiol, 2017). WARS1 is secreted from monocytes into the blood within minutes of infection with pathogenic microorganisms. Through its interaction with the TLR2 and TLR4/myeloid differentiation protein-2 (MD2) complexes on macrophages, it activates an inflammatory response. This leads to the release of cytokines and chemokines, which bring in more neutrophils and remove invading microorganisms.

Innovative drug development strategy targeting WARS1

As excessively secreted WARS1 causes overwhelming pathological inflammation, such as a cytokine storm, it is a promising drug target for potent anti-inflammatory therapeutics. Importantly, WARS1 levels are highly correlated with inflammation and disease severity in patients with various intractable inflammatory disorders.

On the other hand, WARS1 can be used as a possible biomedicine for immunocompromised patients with intractable infections like tuberculosis because it boosts immune function.