Aminoacyl tRNA synthetase-interacting multifunctional protein 1 (AIMP1) has been reported to have antitumor effects in various tumor models. However, mechanisms by which AIMP1 ameliorates tumorigenesis are not well understood. As NK cells are a major cell type involved in antitumor activities and AIMP1 is known to activate professional APCs, we determined whether AIMP1 induced NK cell activation directly or via these APCs. AIMP1 induced the expression of surface activation markers on murine NK cells in total splenocytes, although AIMP1 did not directly induce these activation markers of NK cells. The inductive effect of AIMP1 on NK cell activation disappeared in macrophage-depleted splenocytes, indicating that macrophages were required for the AIMP1-induced activation of NK cells. Furthermore, coculture experiments showed that AIMP1 activated NK cells in the presence of isolated macrophages, but failed to activate NK cells when cultured alone or with dendritic cells or B cells. Although AIMP1 significantly promoted TNF-α production by macrophages, the secreted TNF-α partially affected the NK cell activation. Transwell cocultivation analysis revealed that direct contact between macrophages and NK cells was required for the AIMP1-induced NK cell activation. In addition, AIMP1 significantly enhanced cytotoxicity of NK cells against Yac-1 cells. Furthermore, the in vivo administration of AIMP1 also induced NK cell activation systemically with a macrophage-dependent manner. Importantly, AIMP1 dramatically reduced the lung metastasis of melanoma cells, which was mediated by NK cells. Taken together, our results show that AIMP1 induces antitumor responses by NK cell activation mainly via macrophages.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning, Government of South Korea (Grants NRF-2014R1A2A2A01005031 and NRF-2017R1A2B2009442 and Creative Materials Discovery Program 2016M3D1A1021387), and also by the Agriculture, Food, and Rural Affairs Research Center Support Program, Ministry of Agriculture, Food, and Rural Affairs, Republic of Korea.
© 2017 by The American Association of Immunologists, Inc.
ASJC Scopus subject areas
- Immunology and Allergy