Threonyl-tRNA Synthetase Promotes T Helper Type 1 Cell Responses by Inducing Dendritic Cell Maturation and IL-12 Production via an NF-kappa B Pathway
DC Field | Value | Language |
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dc.contributor.author | Jung, Hak-Jun | - |
dc.contributor.author | Park, Su-Ho | - |
dc.contributor.author | Cho, Kyung-Min | - |
dc.contributor.author | Jung, Kwang Il | - |
dc.contributor.author | Cho, Daeho | - |
dc.contributor.author | Kim, Tae Sung | - |
dc.date.accessioned | 2021-08-30T10:53:26Z | - |
dc.date.available | 2021-08-30T10:53:26Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-10-14 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/52459 | - |
dc.description.abstract | Threonyl-tRNA synthetase (TRS) is an aminoacyl-tRNA synthetase that catalyzes the aminoacylation of tRNA by transferring threonine. In addition to an essential role in translation, TRS was extracellularly detected in autoimmune diseases and also exhibited pro-angiogenetic activity. TRS is reported to be secreted into the extracellular space when vascular endothelial cells encounter tumor necrosis factor-alpha. As T helper (Th) type 1 response and IFN-gamma levels are associated with autoimmunity and angiogenesis, in this study, we investigated the effects of TRS on dendritic cell (DC) activation and CD4 T cell polarization. TRS-treated DCs exhibited up-regulated expression of activation-related cell-surface molecules, including CD40, CD80, CD86, and MHC class II. Treatment of DCs with TRS resulted in a significant increase of IL-12 production. TRS triggered nuclear translocation of the NF-kappa B p65 subunit along with the degradation of I kappa B proteins and the phosphorylation of MAPKs in DCs. Additionally, MAPK inhibitors markedly recovered the degradation of I kappa B proteins and the increased IL-12 production in TRS-treated DCs, suggesting the involvement of MAPKs as the upstream regulators of NF-kappa B in TRS-induced DC maturation and activation. Importantly, TRS-stimulated DCs significantly increased the populations of IFN-gamma(+)CD4 T cells, and the levels of IFN-gamma when co-cultured with CD4(+) T cells. The addition of a neutralizing anti-IL-12 mAb to the cell cultures of TRS-treated DCs and CD4(+) T cells resulted in decreased IFN-gamma production, indicating that TRS-stimulated DCs may enhance the Th1 response through DC-derived IL-12. Injection of OT-II mice with OVA-pulsed, TRS-treated DCs also enhanced Ag-specific Th1 responses in vivo. Importantly, injection with TRS-treated DC exhibited increased populations of IFN-gamma(+)-CD4(+) and -CD8(+) T cells as well as secretion level of IFN-gamma, resulting in viral clearance and increased survival periods in mice infected with influenza A virus (IAV), as the Th1 response is associated with the enhanced cellular immunity, including anti-viral activity. Taken together, these results indicate that TRS promotes the maturation and activation of DCs, DC-mediated Th1 responses, and anti-viral effect on IAV infection. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.subject | IFN-GAMMA | - |
dc.subject | CYTOKINES | - |
dc.subject | KINASES | - |
dc.title | Threonyl-tRNA Synthetase Promotes T Helper Type 1 Cell Responses by Inducing Dendritic Cell Maturation and IL-12 Production via an NF-kappa B Pathway | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cho, Daeho | - |
dc.contributor.affiliatedAuthor | Kim, Tae Sung | - |
dc.identifier.doi | 10.3389/fimmu.2020.571959 | - |
dc.identifier.scopusid | 2-s2.0-85094664732 | - |
dc.identifier.wosid | 000584718300001 | - |
dc.identifier.bibliographicCitation | FRONTIERS IN IMMUNOLOGY, v.11 | - |
dc.relation.isPartOf | FRONTIERS IN IMMUNOLOGY | - |
dc.citation.title | FRONTIERS IN IMMUNOLOGY | - |
dc.citation.volume | 11 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | IFN-GAMMA | - |
dc.subject.keywordPlus | CYTOKINES | - |
dc.subject.keywordPlus | KINASES | - |
dc.subject.keywordAuthor | aminoacyl-tRNA synthetase | - |
dc.subject.keywordAuthor | threonyl-tRNA synthetase | - |
dc.subject.keywordAuthor | dendritic cell | - |
dc.subject.keywordAuthor | interleukin-12 | - |
dc.subject.keywordAuthor | type 1 helper T cells | - |
dc.subject.keywordAuthor | interferon-& | - |
dc.subject.keywordAuthor | #947 | - |
dc.subject.keywordAuthor | influenza A virus | - |
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