AIMP1/p43 protein induces the maturation of bone marrow-derived dendritic cells with T helper type 1-polarizing ability.
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-gamma 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-gamma, 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.
Kim
Eugene
E
School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Kim
Seung Hyun
SH
Kim
Sunghoon
S
Cho
Daeho
D
Kim
Tae Sung
TS
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C514492:Aimp1 protein, mouse; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018664:Interleukin-12; D007371:Interferon-gamma