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* School of Life Sciences and Biotechnology, Korea University;
Center for Medicinal Protein Network and Systems Biology, College of Pharmacy, Seoul National University; and
Department of Life Science and Research Center for Women’s Diseases, Sookmyung Women’s University, Seoul, Republic of Korea
AIMP1 (ARS-interacting multifunctional protein 1), previously known as p43, was initially identified as a factor associated with a macromolecular tRNA synthetase complex. Recently, we demonstrated that AIMP1 is also secreted and acts as a novel pleiotropic cytokine. In this study, we investigated whether AIMP1 induces the activation and maturation of murine bone marrow-derived dendritic cells (DCs). AIMP1-treated DCs exhibited up-regulated expression of cell-surface molecules, including CD40, CD86, and MHC class II. Additionally, microarray analysis and RT-PCR determinations indicated that the expression of known DC maturation genes also increased significantly following treatment with AIMP1. Treatment of DCs with AIMP1 resulted in a significant increase in IL-12 production and Ag-presenting capability, and it also stimulated the proliferation of allogeneic T cells. Importantly, AIMP1-treated DCs induced activation of Ag-specific Th type 1 (Th1) cells in vitro and in vivo. AIMP1-stimulated DCs significantly enhanced the IFN-
production of cocultured CD4+ T cells. Immunization of mice with keyhole limpet hemocyanin-pulsed AIMP1 DCs efficiently led to Ag-specific Th1 cell responses, as determined by flow cytometry and ELISA. The addition of a neutralizing anti-IL-12 mAb to the cell cultures that had been treated with AIMP1 resulted in the decreased production of IFN-, thereby indicating that AIMP1-stimulated DCs may enhance the Th1 response through increased production of IL-12 by APCs. Taken together, these results indicate that AIMP1 protein induces the maturation and activation of DCs, which skew the immune response toward a Th1 response.
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1 This work was supported by grants from the National R&D Program for Cancer Control, Ministry of Health and Welfare (070335) and the Science Research Center Program, Ministry of Science and Technology, Republic of Korea (R11-2005-017-02001-0 to T.S.K.). This work was also supported by a grant from the Korea Science and Engineering Foundation (R17-2007-020-01000-0 to S.H.K.).
2 Address correspondence and reprint requests to Dr. Tae Sung Kim, School of Life Sciences and Biotechnology, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Seoul 136-713, Republic of Korea. E-mail address: tskim{at}korea.ac.kr
3 Abbreviations used in this paper: DC, dendritic cell; AIMP1, ARS-interacting multifunctional protein 1; iDC, immature DC; DC1, type-1 polarized dendritic cell; DC2, type-2 polarized dendritic cell; LN, lymph node; MFI, mean fluorescence intensity; PMB, polymyxin B; SOCS, suppressor of cytokine signaling.
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