Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction - A comparative study

被引：26
作者：
Adnan, Endy [1 ]
Matsumoto, Takuya [1 ]
Ishizaki, Jun [1 ]
Onishi, Sachiko [1 ]
Suemori, Koichiro [1 ]
Yasukawa, Masaki [1 ]
Hasegawa, Hitoshi [1 ]
机构：
[1] Ehime Univ, Grad Sch Med, Dept Hematol Clin Immunol & Infect Dis, Toon, Ehime 7910295, Japan
来源：
CLINICAL IMMUNOLOGY | 2016年 / 173卷
关键词：
Dendritic cells; Tolerance; Protein kinase C inhibitor; Regulatory T cells; PROLIFERATOR-ACTIVATED-RECEPTOR; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CLASSIFICATION CRITERIA; MATURATION; DIFFERENTIATION; MOLECULES; VITAMIN-D-3; MODULATION; TOLERANCE; CCR7;
D O I：
10.1016/j.clim.2016.09.007
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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)-beta, and a combination of peroxisome proliferator-activated receptor gamma agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-beta-, 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 Sjogren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码：96 / 108
页数：13
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