Adnan Endy, Matsumoto Takuya, Ishizaki Jun, Onishi Sachiko, Suemori Koichiro, Yasukawa Masaki, Hasegawa Hitoshi
Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Clin Immunol. 2016 Dec;173:96-108. doi: 10.1016/j.clim.2016.09.007. Epub 2016 Sep 19.
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.
耐受性树突状细胞（tDCs）是特异性诱导免疫耐受的一种很有前景的治疗工具。人tDCs可在体外使用各种化合物生成。然而，最适合临床应用的化合物仍未明确。我们比较了用蛋白激酶C抑制剂（PKCI）、地塞米松、维生素D3（Vit D3）、雷帕霉素（Rapa）、白细胞介素（IL）-10、转化生长因子（TGF）-β以及过氧化物酶体增殖物激活受体γ激动剂与视黄酸组合处理的tDCs的耐受性特性。所有tDCs均具有半成熟的DC表型。PKCI -、TGF -β-和Rapa - tDCs表现出CCR7表达并迁移至CCL19，但其他tDCs表现出很少或没有。PKCI -和IL -10 - tDCs比其他tDCs更强烈地诱导功能性调节性T细胞。所有tDCs的耐受性特性对促炎刺激稳定。此外，PKCI - tDCs由类风湿性关节炎和原发性干燥综合征患者产生。因此，PKCI - tDCs表现出最适合耐受性诱导治疗的特性。
