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

Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses. Cell Mol Immunol. 2019 Dec 04;: Authors: Adams RA, Fernandes-Cerqueira C, Notarnicola A, Mertsching E, Xu Z, Lo WS, Ogilvie K, Chiang KP, Ampudia J, Rosengren S, Cubitt A, King DJ, Mendlein JD, Yang XL, Nangle LA, Lundberg IE, Jakobsson PJ, Schimmel P 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+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive d...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research