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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 | Global malaria mortality between 1980 and 2010: a systematic analysis显示文摘 | Christopher JL Murray Lisa C Rosenfeld Stephen S Lim Kathryn G Andrews Kyle J Foreman Diana Haring Nancy Fullman Mohsen Naghavi Rafael Lozano Alan D Lopez | 2012 | The Lancet2012，，9814： | 2 |
| 3 | Gas-liquid-solid operation of a vortex-ingesting stirred tank reactor显示文摘 | Conway K Kyle A Rielly C D | 2002 | Chemical Engineering Research and Design2002，80，8： | 1 |
| 4 | Lysine metabolism by the mammary gland of lactating goats at two stages of lactation显示文摘 | Mabjeesh S J Kyle C E Macrae J C | 2000 | Journal of Dairy Science2000，83，： | 1 |
| 5 | Most mammalian mRNAs are conserved targets of microRNAs显示文摘 | Robin C F Kyle K F Christopher B B | 2009 | Genome Research2009，19，： | 1 |
| 6 | Analysis of trace elements including rare earth elements in fluid inclusion liquids 显示文摘 | Norman D I Kyle P R Baron C | 1989 | Econ Geol1989，84，1： | 1 |
| 7 | Nutritional assessment: lean body mass depletion at hospital admission is associated with an increased length of stay 显示文摘 | Pichard C Kyle UG Morabia A | 2004 | Am J Clin Nutr2004，79，4： | 1 |
| 8 | Screw position affects dynamic compression plate strain in an in vitro fracture model 显示文摘 | Ellis T Bourgeault C A Kyle R F | 2001 | J Orthop Trauma2001，15，5： | 1 |
| 9 | Prognostic value of the serum-free light chain ratio in patients with newly diagnosed myeloma and proposed incorporation into the International Staging System显示文摘 | Snozek C L Katzmann J A Kyle R A | 2008 | Leukemia2008，22，10： | 1 |
| 10 | Response of soybean accessions from provinces in southern China to Phytophthora sojae 显示文摘 | Kyle D E Nickell C D Nelson R L | 1998 | Plant Disease1998，82，： | 1 |
| 11 | Pre concentration of benzalkonium chloride using sodium dodecyl sulfate attached to a strong anion exchange resin显示文摘 | KYLE A J ELIZABETH G V ERIC D C | 1999 | Functional Polymers1999，40，： | 1 |
| 12 | pfcrt Allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines显示文摘 | Chen N Kyle DE Pasay C | 2003 | Antimicrob Agents Chemother2003，47，11： | 1 |
| 13 | The featuregate model of visual selection 显示文摘 | KYLE R C | 1999 | Psychological Research1999，62，23： | 1 |
| 14 | Vascular sources of amino acids for milk protein synthesis in goats at two stages of lactation显示文摘 | Mabjeesh S J Kyle C E MacRae J C | 2002 | J Dairy Sci2002，85，4： | 1 |
| 15 | Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines 显示文摘 | DELANEY C A WANG L Z KYLE S | 2000 | Clin Cancer Res2000，6，7： | 1 |
| 16 | Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients 显示文摘 | Pichard C Kyle UG Janssens JP | 1997 | Nutrition1997，13，： | 1 |
| 17 | Global malaria mortality between 1980 and 2010: a systematic analysis显示文摘 | Christopher JL Murray Lisa C Rosenfeld Stephen S Lim Kathryn G Andrews Kyle J Foreman Diana Haring Nancy Fullman Mohsen Naghavi Rafael Lozano Alan D Lopez | 2012 | 2012 (9814)2012，，9814： | 1 |
| 18 | Response of soybean accessions from provinces in southern China to Phytophthora sojae 显示文摘 | Kyle D E Nickell C D Nelson R L | 1998 | Plant Disease1998，82，： | 1 |
| 19 | Lysine metabolism by the mammary gland of lactating goats at two stages of lactation显示文摘 | Mabjeesh S J Kyle C E Macrae J C Bequette B J | 2000 | Journal of Dairy Science2000，83，： | 1 |
| 20 | Surgical treatment of intertrochanteric hip fractures with associated femoral neck fractures using a sliding hip screw 显示文摘 | Kyle R F Ellis T J Templeman D C | 2005 | J Orthop Trauma2005，19，1： | 1 |
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