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KMID : 0923620200200050038
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Immune Network
2020 Volume.20 No. 5 p.38 ~ p.38
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Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells
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Park Hui-Won
Park Sun-Hee
Jo Hyeon-Ju
Kim Tae-Gyu
Lee Jeong-Hyun
Kang Seung-Goo
Jang Young-Saeng
Kim Pyeung-Hyeun
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Abstract
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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.
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KEYWORD
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Lactoferrin, Dendritic cells, B7 antigens, Immune tolerance, Regulatory T cells, Suppressive factor
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