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.

中文翻译：

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乳铁蛋白诱导耐受性骨髓衍生树突细胞

树突状细胞 (DC) 是专职抗原呈递细胞 (APC)，可启动 T 细胞反应和耐受性。致耐受性 DCs (tDCs) 是调节性 DCs，通过诱导 T 细胞无反应性和 Tregs 来抑制免疫反应。由于已证明乳铁蛋白 (LF) 可诱导功能性 Treg 并具有针对炎症性肠病的保护作用，因此我们探索了 LF 对小鼠骨髓衍生 DC (BMDC) 的致耐受作用。CD80/86 和 MHC II 类的表达在 LF 处理的 BMDCs (LF-BMDCs) 中减少。LF 促进 BMDCs 在卵清蛋白特异性 CD4+ T 细胞培养物中抑制增殖并提高 Foxp3+ 诱导的 Treg (iTreg) 分化。Foxp3 表达通过使用 CTLA4-Ig 阻断 B7 分子而进一步增加，但通过使用抗 CD28 Ab 的额外 CD28 刺激而减少。另一方面，LF-BMDC 中精氨酸酶-1 和吲哚胺 2,3-双加氧酶-1（称为关键 T 细胞抑制分子）的水平增加。一致地，这些分子的抑制剂部分恢复了 LF-BMDCs 的抑制活性。总的来说，这些结果表明，LF 通过抑制 T 细胞增殖和增强 iTreg 分化，有效地使 DC 具有耐受性。LF 的这种致耐受效应是由于共刺激分子的减少和抑制分子的增强。这些结果表明，LF 通过抑制 T 细胞增殖和增强 iTreg 分化，有效地使 DC 具有耐受性。LF 的这种致耐受效应是由于共刺激分子的减少和抑制分子的增强。这些结果表明，LF 通过抑制 T 细胞增殖和增强 iTreg 分化，有效地使 DC 具有耐受性。LF 的这种致耐受效应是由于共刺激分子的减少和抑制分子的增强。