Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (Ape1/Ref-1) Modulates Antigen Presenting Cell-mediated T Helper Cell Type 1 Responses
| Autor: | Yuji Takeda, Naoto Ishii, Hironobu Asao, Naoki Asao, Akemi Araki, Hidetoshi Nara, Nasrin Akhter |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Immunology Antigen-Presenting Cells Biology Biochemistry Interferon-gamma 03 medical and health sciences 0302 clinical medicine Immune system Benzoquinones DNA-(Apurinic or Apyrimidinic Site) Lyase medicine Animals Antigen-presenting cell Molecular Biology Cells Cultured CD86 Immunity Cellular Cell Biology Dendritic cell T helper cell Th1 Cells Interleukin-12 DNA-(apurinic or apyrimidinic site) lyase Molecular biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Propionates Cell activation Oxidation-Reduction CD80 |
| Zdroj: | Journal of Biological Chemistry. 291:23672-23680 |
| ISSN: | 0021-9258 |
| Popis: | Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) is a multifunctional protein possessing DNA repair, redox control, and transcriptional regulatory activities. Although Ape1/Ref-1 plays multiple roles in the immune system, its functions in helper T (Th) cell activation and differentiation are largely unknown. In this study, the function of Ape1/Ref-1 in Th cell activation was analyzed using an Ape1/Ref-1 redox-specific inhibitor, E3330. When splenocytes from OT-II mice, which are ovalbumin (OVA)-specific T-cell receptor transgenic mice, were activated with OVA in the presence of E3330, the induction of IFN-γ-producing OT-II T cells was significantly increased. In contrast, E3330 did not enhance IFN-γ production from plate-bound anti-CD3 antibody-stimulated CD4+ T cells in the absence of antigen presenting cells (APCs). Furthermore, E3330-pretreated and OVA-pulsed APCs also enhanced the IFN-γ production from OT-II T cells. These results suggested that E3330 enhances Th1 responses by modifying APC function. E3330 did not alter the surface expression of MHC-II or the co-stimulatory molecules CD80 and CD86 on APCs. On the other hand, E3330 up-regulated the IL-12 p35 and p40 gene expression, and IL-12 surface retention, but decreased the IL-12 secretion from Toll-like receptor (TLR) ligand-stimulated APCs. These results were confirmed with Ape1/Ref-1 knockdown experiments. Taken together, our findings indicated that the suppression of Ape1/Ref-1 redox function leads to an increased cell surface retention of IL-12 and enhances Th1 responses. This is the first study to demonstrate that Ape1/Ref-1 modulates the IL-12 production and secretion from APCs and controls Th1 immune responses. |
| Databáze: | OpenAIRE |
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