title: Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists.
abstract: The major limitation for the maturation of dendritic cells (DCs) using Toll-like receptor (TLR) agonists is their decreased ability to migrate into lymph nodes compared with conventional DCs. CD38 can be used as a multifunctional marker to modulate migration, survival and Th1 responses of DCs. CD74 has been shown to negatively regulate DC migration. The goal of this study was to investigate the combinations of TLR agonists and interferons (IFNs) that most effectively regulate CD38 and CD74 expression on DCs. Synergistic TLR agonist stimulation in combination with IFN-α and IFN-γ was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of IL-12p70. An in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability, similar to that observed in cells expressing CD38, CD74 and CCR7. The results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, Korea.
authors.forename: Thanh-Nhan
authors.initials: TN
authors.lastname: Nguyen-Pham
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Lim
authors.forename: Truc Anh Thi
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Chun-Ji
authors.initials: CJ
authors.lastname: Jin
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Cheol Yi
authors.initials: CY
authors.lastname: Hong
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis* / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D054400:Receptors, CCR7; D051193:Toll-Like Receptors; C045084:invariant chain; D018664:Interleukin-12; D007371:Interferon-gamma; D051997:ADP-ribosyl Cyclase 1