Correction: Corrigendum: Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

Ahn, Young Ha; Park, Sunyoung; Choi, Jeong June; Park, Bo Kyung; Rhee, Kyu-Nam; Kang, Eunjoo; Ahn, Soyeon; Lee, Chul‐Ho; Lee, Jong Soo; Cho, Mi La; Park, Sung Hwan; Park, Kyunghee; Park, Hye Jung; Lee, Jae Hyun; Kwon, Nam Hoon; Shim, Hyunbo; Han, Byung Woo; Kim, Pilhan; Lee, Joo Youn; Jeon, Young-Ho; Huh, Jin Won; Mirim, Jin; Kim, Sung‐Hoon

doi:10.1038/nmicrobiol.2017.15

Cited by 3 publications

(5 citation statements)

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“…As a therapeutic modality, we created an anti-human WARS1 monoclonal IgG1 antibody (anti-WARS1 MAb) that has subnanomolar affinity for N -terminal active domain of human, marmoset, and mouse WARS1 (Fig. EV4 ) (Ahn et al, 2017 ). To test the neutralizing activity of the anti-WARS1 MAb, we used marmosets, considering the high similarity between human and non-human primate (NHP) inflammatory responses (Nelson and Loveday, 2014 ; ’t Hart et al, 2004 ).…”

Section: Resultsmentioning

confidence: 99%

“…Tryptophanyl tRNA synthetase 1 (WARS1), one of aminoacyl tRNA synthetases (ARSs), is classically known as an essential housekeeping enzyme that ligates tryptophan to its cognate tRNA for protein synthesis (Jin, 2019 ; Kwon et al, 2019 ). Interestingly, when there is a pathogenic infection, WARS1 is promptly released from monocytes into the extracellular space (Ahn et al, 2017 ; Nguyen et al, 2023 ). The secreted WARS1 turns on TLR2 and TLR4/myeloid differentiation factor-2 (MD-2) signaling to boost innate inflammatory responses (Ahn et al, 2017 ); the production of cytokines and chemokines such as TNF-α, IL-6, IL-8, and MIP-1α (Lee et al, 2019 ; Nguyen et al, 2020 ); and neutrophil infiltration.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, when there is a pathogenic infection, WARS1 is promptly released from monocytes into the extracellular space (Ahn et al, 2017 ; Nguyen et al, 2023 ). The secreted WARS1 turns on TLR2 and TLR4/myeloid differentiation factor-2 (MD-2) signaling to boost innate inflammatory responses (Ahn et al, 2017 ); the production of cytokines and chemokines such as TNF-α, IL-6, IL-8, and MIP-1α (Lee et al, 2019 ; Nguyen et al, 2020 ); and neutrophil infiltration. Patients with sepsis have been found to have high levels of WARS1 in their blood (Ahn et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…The secreted WARS1 turns on TLR2 and TLR4/myeloid differentiation factor-2 (MD-2) signaling to boost innate inflammatory responses (Ahn et al, 2017 ); the production of cytokines and chemokines such as TNF-α, IL-6, IL-8, and MIP-1α (Lee et al, 2019 ; Nguyen et al, 2020 ); and neutrophil infiltration. Patients with sepsis have been found to have high levels of WARS1 in their blood (Ahn et al, 2017 ). WARS1 has also been reported to be a biomarker for predicting death in sepsis (Choi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis

Kim,

Huh,

Choi

et al. 2023

EMBO Mol Med

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Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis

Kim,

Huh,

Choi

et al. 2023

EMBO Mol Med

Self Cite

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“…Rapid secretion of WARS results from pathogen infection and serves to prime the innate immune system, bind to macrophages to induce phagocytosis and chemokine production. WARS has been demonstrated to have as much as an 18 fold increase 2 h post infection [ 18 ]. In addition, WARS has an immunomodulatory function with the capacity to be hijacked by pathogenic invaders seeking to evade intracellular detection via control of T-cell proliferation, followed by exhaustion [ 11 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease

Bustamante

Yau

Boys

et al. 2022

IJMS

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The epithelial barrier’s primary role is to protect against entry of foreign and pathogenic elements. Both COVID-19 and Inflammatory Bowel Disease (IBD) show commonalities in symptoms and treatment with sensitization of the epithelial barrier inviting an immune response. In this study we use a multi-omics strategy to identify a common signature of immune disease that may be able to predict for more severe patient outcomes. Global proteomic approaches were applied to transcriptome and proteome. Further semi- and relative- quantitative targeted mass spectrometry methods were developed to substantiate the proteomic and metabolomics changes in nasal swabs from healthy, COVID-19 (24 h and 3 weeks post infection); serums from Crohn’s disease patients (scored for epithelial leak), terminal ileum tissue biopsies (patient matched inflamed and non-inflamed regions, and controls). We found that the tryptophan/kynurenine metabolism pathway is a ‘hub’ regulator of canonical and non-canonical transcription, macrophage release of cytokines and significant changes in the immune and metabolic status with increasing severity and disease course. Significantly modified pathways include stress response regulator EIF2 signaling (p = 1 × 10−3); energy metabolism, KYNU (p = 4 × 10−4), WARS (p = 1 × 10−7); inflammation, and IDO activity (p = 1 × 10−6). Heightened levels of PARP1, WARS and KYNU are predictive at the acute stage of infection for resilience, while in contrast, levels remained high and are predictive of persistent and more severe outcomes in COVID disease. Generation of a targeted marker profile showed these changes in immune disease underlay resolution of epithelial barrier function and have the potential to define disease trajectory and more severe patient outcomes.

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WARS1 and SARS1 : Two tRNA synthetases implicated in autosomal recessive microcephaly

et al. 2022

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Correction: Corrigendum: Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

Abstract: © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

Cited by 3 publications

References 0 publications

Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis

Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis

Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease

WARS1 and SARS1 : Two tRNA synthetases implicated in autosomal recessive microcephaly

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