{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:27:02Z","timestamp":1777498022180,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In addition to essential roles in protein synthesis, lysyl\u2013tRNA synthetase (KRS) is secreted to trigger a proinflammatory function that induces macrophage activation and TNF-\u03b1 secretion. KRS has been associated with autoimmune diseases such as polymyositis and dermatomyositis. In this study, we investigated the immunomodulatory effects of KRS on bone marrow\u2013derived dendritic cells (DCs) of C57BL\/6 mice and subsequent polarization of Th cells and analyzed the underlying mechanisms. KRS-treated DCs increased the expression of cell surface molecules and proinflammatory cytokines associated with DC maturation and activation. Especially, KRS treatment significantly increased production of IL-12, a Th1-polarizing cytokine, in DCs. KRS triggered the nuclear translocation of the NF-\u03baB p65 subunit along with the degradation of I\u03baB proteins and the phosphorylation of MAPKs in DCs. Additionally, JNK, p38, and ERK inhibitors markedly recovered the degradation of I\u03baB proteins, suggesting the involvement of MAPKs as the upstream regulators of NF-\u03baB in the KRS-induced DC maturation and activation. Importantly, KRS-treated DCs strongly increased the differentiation of Th1 cells when cocultured with CD4+ T cells. The addition of anti\u2013IL-12\u2013neutralizing Ab abolished the secretion of IFN-\u03b3 in the coculture, indicating that KRS induces Th1 cell response via DC-derived IL-12. Moreover, KRS enhanced the OVA-specific Th1 cell polarization in vivo following the adoptive transfer of OVA-pulsed DCs. Taken together, these results indicated that KRS effectively induced the maturation and activation of DCs through MAPKs\/NF-\u03baB\u2013signaling pathways and favored DC-mediated Th1 cell response.<\/jats:p>","DOI":"10.4049\/jimmunol.1800386","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T13:35:21Z","timestamp":1538400921000},"page":"2832-2841","source":"Crossref","is-referenced-by-count":14,"title":["Lysyl\u2013Transfer RNA Synthetase Induces the Maturation of Dendritic Cells through MAPK and NF-\u03baB Pathways, Strongly Contributing to Enhanced Th1 Cell Responses"],"prefix":"10.1093","volume":"201","author":[{"given":"Hui Xuan","family":"Lim","sequence":"first","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1972-2305","authenticated-orcid":false,"given":"Hak-Jun","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arim","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-7808","authenticated-orcid":false,"given":"Si Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7571-3791","authenticated-orcid":false,"given":"Byung Woo","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University , Seoul 08826 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daeho","family":"Cho","sequence":"additional","affiliation":[{"name":"Institute of Convergence Science, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University , Seoul 02841 ,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"2025030417573915100_r1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/128_2013_476","article-title":"Extracellular activities of aminoacyl-tRNA synthetases: new mediators for cell-cell communication","volume":"344","author":"Son","year":"2014","journal-title":"Top. 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