Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC.
Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC.
复制标题
通过同时使用耐受性 DC 和 MSC 来协同抑制自身免疫性关节炎
DOI：
10.1038/srep43188
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发表时间：
2017-02-23
影响因子：
4.6
通讯作者：
Min W
中科院分区：
文献类型：
--
作者：
Li R;Zhang Y;Zheng X;Peng S;Yuan K;Zhang X;Min W
类风湿性关节炎（RA）是一种以进行性免疫介导的关节退化为特征的自身免疫性疾病。目前的治疗不是抗原特异性的，并且与各种不良反应相关。我们先前已经证明，致耐受性树突状细胞（Tol-DC）是有效的抗原特异性免疫调节剂，在自身免疫性疾病的免疫治疗中具有很大的前景。在这项研究中，我们的目标是通过结合Tol-DC和间充质干细胞（MSC）开发新的免疫疗法。我们证明了RelB基因沉默导致抑制T细胞应答并选择性地促进Treg产生的Tol-DC的产生。MSC的组合在抑制T细胞应答中协同Tol-DC的致耐受性能力。在鼠胶原诱导的关节炎（CIA）模型中，我们证明了施用RelB基因沉默的Tol-DC或MSC抑制关节炎的进展。联合应用Tol-DC和MSC的同时治疗显著增强了这种治疗效果，如临床症状改善、临床评分降低和关节损伤减轻所证明的。这些治疗效果与抑制CII特异性T细胞反应、Th极化和抑制促炎细胞因子以及减少软骨变性有关。这项研究首次证明了一种治疗自身免疫性炎性关节疾病的新方法，同时治疗RelB基因沉默的Tol-DC和MSC。
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC.