凋亡细胞处理的树突状细胞静脉输注通过阻断 Th17 细胞活性诱导免疫耐受。
Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity.
机构信息
Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA.
出版信息
Immunobiology. 2013 Aug;218(8):1069-76. doi: 10.1016/j.imbio.2013.02.003. Epub 2013 Mar 1.
Abstract
Apoptotic cell-induced tolerogenic dendritic cells (DCs) play an important role in induction of peripheral tolerance in vivo; however, the mechanisms of immune tolerance induced by these DCs are poorly understood. Here we show that treatment of apoptotic cells modulates expression of inflammation- and tolerance-associated molecules including Gr-1, B220, CD205 and galectin-1 on bone marrow-derived DCs. In addition, apoptotic cell-treated DCs suppress secretion of cytokines produced by Th17 cells. Our data also demonstrate that i.v. transfer of apoptotic cell-treated DCs blocks EAE development and down-regulates production of inflammatory cytokines such as IL-17A and IL-17F in CD4+ T cells. These results suggest that apoptotic cell-treated DCs may inhibit activity of Th17 cells via down-regulation of inflammatory cytokine production, thereby affecting EAE development in vivo. Our results reveal a potential mechanism of immune tolerance mediated by apoptotic cell-treated DCs and the possible use of apoptotic cell-treated DCs to treat autoimmune diseases such as MS/EAE.
摘要
凋亡细胞诱导的耐受性树突状细胞（DC）在体内诱导外周耐受中发挥重要作用；然而，这些 DC 诱导免疫耐受的机制尚不清楚。在这里，我们发现凋亡细胞的处理可调节骨髓来源的 DC 上炎症和耐受相关分子的表达，包括 Gr-1、B220、CD205 和半乳糖凝集素-1。此外，凋亡细胞处理的 DC 可抑制 Th17 细胞产生的细胞因子的分泌。我们的数据还表明，静脉注射凋亡细胞处理的 DC 可阻断 EAE 的发展，并下调 CD4+T 细胞中炎症细胞因子如 IL-17A 和 IL-17F 的产生。这些结果表明，凋亡细胞处理的 DC 可能通过下调炎症细胞因子的产生来抑制 Th17 细胞的活性，从而影响体内 EAE 的发展。我们的结果揭示了凋亡细胞处理的 DC 介导免疫耐受的潜在机制，以及使用凋亡细胞处理的 DC 治疗自身免疫性疾病（如 MS/EAE）的可能性。
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