Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses.

ABSTRACT: His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4⁺ and CD8⁺

SUBMITTER: Adams RA 

PROVIDER: S-EPMC8166958 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature