title: Minocycline promotes the generation of dendritic cells with regulatory properties.
abstract: Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse bone marrow (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion. Mino-DCs also show decreased ability to prime allogeneic-specific T cells, while increasing the expansion of CD4+CD25+Foxp3+ T regulatory cells both in vitro and in vivo. In addition, pretreatment with MOG35-55 peptide-pulsed Mino-DCs ameliorates clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Narae
authors.initials: N
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Chan-Su
authors.initials: CS
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Im
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Ji-Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Sukgil
authors.initials: S
authors.lastname: Song
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D005260:Female; D007959:Lymphocyte Culture Test, Mixed; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000276:immunology / Q000494:pharmacology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D008911:Minocycline
keywords: CD4 Tregs; Immune response; Immunity; Immunology and Microbiology Section; dendritic cell; growth promotion; minocycline; regulatory property