Lysyl-transfer RNA synthetase induces the maturation of dendritic cells through MAPK and NF-κB pathways, strongly contributing to enhanced Th1 cell responses

Hui Xuan Lim, Hak Jun Jung, Arim Lee, Si Hoon Park, Byung Woo Han, Daeho Cho, Tae Sung Kim

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


In addition to essential roles in protein synthesis, lysyl-tRNA synthetase (KRS) is secreted to trigger a proinflammatory function that induces macrophage activation and TNF-a 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-derived 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-κB p65 subunit along with the degradation of IkB proteins and the phosphorylation of MAPKs in DCs. Additionally, JNK, p38, and ERK inhibitors markedly recovered the degradation of IkB proteins, suggesting the involvement of MAPKs as the upstream regulators of NF-κB 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-IL-12-neutralizing Ab abolished the secretion of IFN-g 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-κB-signaling pathways and favored DC-mediated Th1 cell response.

Original languageEnglish
Pages (from-to)2824-2831
Number of pages8
JournalJournal of Immunology
Issue number9
Publication statusPublished - 2018 Nov 1

Bibliographical note

Funding Information:
This work was supported by a grant from the National Institutes of Health (R01 AI25640).

Publisher Copyright:
© 2018 by The American Association of Immunologists, Inc.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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