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| 1 | Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses显示文摘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 disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome. | Ryan AAdams Cátia Fernandes-Cerqueira Antonella Notarnicola Elisabeth Mertsching Zhiwen Xu Wing-Sze Lo Kathleen Ogilvie Kyle PChiang Jeanette Ampudia Sanna Rosengren Andrea Cubitt David JKing John DMendlein Xiang-Lei Yang Leslie ANangle Ingrid ELundberg Per-Johan Jakobsson Paul Schimmel | 2021 | Cellular & Molecular Immunology2021，18，6： | 2 |
| 2 | Enterovirus myocarditis as a cause of neonatal collapse 显示文摘 | Inwald D Franklin O Cubitt D | 2004 | Arch Dis Child Fetal Neonatal Ed2004，89，5： | 1 |
| 3 | Improved green fluorescence显示文摘 | Heim R Cubitt AB Tsien RY | 1995 | Nature1995，373，： | 1 |
| 4 | Sequence and genome organization of Borna disease virus显示文摘 | Cubitt B Oldstone C de-la-Torre JC | 1994 | J Virol1994，68，3： | 1 |
| 5 | Improved green fluorescence 显示文摘 | HEIM R CUBITT A B AND TSIEN R Y | 1995 | Nature1995，0373，6516： | 1 |
| 6 | Borna disease virus (BDV),a non- segmented RNA virus, replicates in the nuclei of infected cells where infectious BDV ribonucleoproteins are present 显示文摘 | Cubitt B De La Torre JC | 1994 | J Virol1994，68，3： | 1 |
| 7 | Crystal structure of the Aequorea victoria green fluorescent protein 显示文摘 | Ormo M Cubitt A B Kallio K | 1996 | Science1996，273，5280： | 1 |
| 8 | Diversity of en- teric viruses detected in patients with gastroentcritis in a tertiary referral paediatric hospital 显示文摘 | Gallimore CI Cubitt DM Richards AF | 2004 | J Med Virol2004，73，3： | 1 |
| 9 | Crystal structure of the aequorea victoria green fluorescent protein显示文摘 | Orm M Cubitt AB Kallio K | 1996 | Science1996，273，： | 1 |
| 10 | Understanding,improving and using green fluoresscent proteins显示文摘 | Cubitt AB Heim R Adams SR | 1995 | Trends Biochem Sci1995，20，11： | 1 |
| 11 | The Geological Implication of Steady- State Meehanisms in Catastrophe Theory 显示文摘 | John M Cubitt Brian show | 1976 | Mathematical Geology1976，8，6： | 1 |
| 12 | The geological implication of steady-state mechanisms in catastrophe theory 显示文摘 | CUBITT J M SHAW B | 1976 | Mathematical Geology1976，8，6： | 1 |
| 13 | Successful heart transplantation following neonatal necrotic enterovirus myocarditis显示文摘 | Simmonds J Cubitt D Ashworth M | 2008 | Pediatr Cardiol2008，29，4： | 1 |
| 14 | IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes显示文摘 | Cubitt CL Tang Q Monteiro CA Lausch RN Oakes JE | 1993 | Invest Ophthalmol Vis Sci1993，34，11： | 1 |
| 15 | Differences in interleukin-6 gene expression between cultured human corneal epithelial cells and fibroblasts 显示文摘 | Cubitt CL Lausch RN Oakes JE | 1995 | Invest Ophthalmol Vis Sci1995，36，10： | 1 |
| 16 | MK-2206, an Akt inhibitor, enhances carboplatinum/paclitaxel efficacy in gastric cancer cell lines显示文摘 | Almhanna K Cubitt CL Zhang S | 2013 | Cancer Biol Ther2013，14，10： | 1 |
| 17 | Differential regulation of granulocytemacrophage colony stimulation factor gene expression in human corneal cells by proinflammatory cytokines 显示文摘 | Cubitt CL Lausch RN Oakes JE | 1994 | J Immunol1994，153，1： | 1 |
| 18 | Diversity of enteric vi-ruses detected in patients with gastroentcrit is in a tertiary referral pae-diatric hospital显示文摘 | Gallimore CI Cubitt DM Richards AF | 2004 | J Med Virol2004，73，3： | 1 |
| 19 | Combination of HDAC and topoisomerase inhibitors in small cell lung cancer 显示文摘 | Gray J Cubitt C L Zhang S | 2012 | Cancer Biol Ther2012，13，8： | 1 |
| 20 | Crystal structure of the Aequorea Victoria green fluorescent Protein 显示文摘 | OROM M CUBITT A B KALLIO K | 1996 | Science1996，273，： | 1 |
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