title: Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction - A comparative study.
abstract: Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Endy
authors.initials: E
authors.lastname: Adnan
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishizaki
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Onishi
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Suemori
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan. Electronic address: hitoshih@m.ehime-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D012859:Sjogren's Syndrome / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D016207:Cytokines; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D016212:Transforming Growth Factor beta; D002762:Cholecalciferol; D014212:Tretinoin; D003907:Dexamethasone; D011493:Protein Kinase C; D020123:Sirolimus
keywords: Dendritic cells; Protein kinase C inhibitor; Regulatory T cells; Tolerance