Immune Netw.  2020 Oct;20(5):e38. 10.4110/in.2020.20.e38.

Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

• Park HW
• Park SH
• Jo HJ
• Kim TG
• Lee JH
• Kang SG
• Jang YS
• Kim PH

• KMID: 2511860
• DOI: http://doi.org/10.4110/in.2020.20.e38

Abstract

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.

Keyword

Lactoferrin; Dendritic cells; B7 antigens; Immune tolerance; Regulatory T cells; Suppressive factor