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  • 제20권5호
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  • Pages.38.1-38.12
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  • 2020
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

  • Hui-Won Park (Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University) ;
  • Sun-Hee Park (Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University) ;
  • Hyeon-Ju Jo (Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University) ;
  • Tae-Gyu Kim (Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University) ;
  • Jeong Hyun Lee (Department of Systems Immunology, School of Biomedical Science, Kangwon National University) ;
  • Seung-Goo Kang (Department of Systems Immunology, School of Biomedical Science, Kangwon National University) ;
  • Young-Saeng Jang (Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Pyeung-Hyeun Kim (Institute of Bioscience and Biotechnology, Kangwon National University)
  • 투고 : 2020.06.16
  • 심사 : 2020.07.13
  • 발행 : 2020.10.31
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초록

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3+ induced Treg (iTreg) differentiation in ovalbumin-specific CD4+ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

키워드

과제정보

This work was supported by a National Research Foundation of Korea (NRF) grant (NRF-2016R1D1A3B03936377 and NRF-2019R1I1A1A01043808 to YS Jang, NRF-2019R1I1A3A01048952 to PH Kim) and a 2016 Research Grant from Kangwon National University to PH Kim.

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