PMID- 33163246 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201112 IS - 1598-2629 (Print) IS - 2092-6685 (Electronic) IS - 1598-2629 (Linking) VI - 20 IP - 5 DP - 2020 Oct TI - Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells. PG - e38 LID - 10.4110/in.2020.20.e38 [doi] LID - e38 AB - 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. CI - Copyright (c) 2020. The Korean Association of Immunologists. FAU - Park, Hui-Won AU - Park HW AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Park, Sun-Hee AU - Park SH AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Jo, Hyeon-Ju AU - Jo HJ AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Kim, Tae-Gyu AU - Kim TG AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Lee, Jeong Hyun AU - Lee JH AUID- ORCID: 0000-0002-2801-3677 AD - Department of Systems Immunology, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Kang, Seung-Goo AU - Kang SG AUID- ORCID: 0000-0003-3981-1399 AD - Department of Systems Immunology, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Jang, Young-Saeng AU - Jang YS AUID- ORCID: 0000-0001-9844-2074 AD - Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea. AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. FAU - Kim, Pyeung-Hyeun AU - Kim PH AUID- ORCID: 0000-0002-2808-5822 AD - Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea. AD - Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea. LA - eng PT - Journal Article DEP - 20200729 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC7609161 OTO - NOTNLM OT - B7 antigens OT - Dendritic cells OT - Immune tolerance OT - Lactoferrin OT - Regulatory T cells OT - Suppressive factor COIS- Conflicts of Interest: The authors declare no potential conflicts of interest. EDAT- 2020/11/10 06:00 MHDA- 2020/11/10 06:01 PMCR- 2020/10/01 CRDT- 2020/11/09 05:32 PHST- 2020/06/16 00:00 [received] PHST- 2020/07/08 00:00 [revised] PHST- 2020/07/13 00:00 [accepted] PHST- 2020/11/09 05:32 [entrez] PHST- 2020/11/10 06:00 [pubmed] PHST- 2020/11/10 06:01 [medline] PHST- 2020/10/01 00:00 [pmc-release] AID - 2020200503 [pii] AID - 10.4110/in.2020.20.e38 [doi] PST - epublish SO - Immune Netw. 2020 Jul 29;20(5):e38. doi: 10.4110/in.2020.20.e38. eCollection 2020 Oct.