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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.
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Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.

机译：经过基因工程改造以表达IL-10的树突状细胞在实验性哮喘中诱导持久的抗原特异性耐受。

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摘要

Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4(+)CD25(+)Foxp3(+)IL-10(+) regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4(+) mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy.
机译：树突状细胞（DC）是专业的APC，具有独特的能力来启动主要的免疫反应，包括致耐受性反应。我们对基因工程的骨髓来源的DC进行了基因改造，以表达免疫抑制性细胞因子IL-10，并测试了这些细胞控制实验性哮喘的能力。在OVA致敏和攻击前，向未处理的小鼠单次气管内注射OVA刺激的IL-10转导的DC（OVA-IL-10-DC）可阻止气道过敏的所有基本特征，即嗜酸性气道炎症，气道高反应性，和生产黏液，Ag特异性Igs和IL-4。 OVA-IL-10-DC还可以逆转已建立的实验性哮喘，并具有持久的和Ag特异性作用。我们还显示，通过使用IL-10缺陷型小鼠，介导OVA-IL-10-DC的免疫调节作用需要宿主IL-10，并证明OVA特异性CD4（+）CD25的百分比显着增加注射OVA-IL-10-DC的小鼠纵隔淋巴结中的（+）Foxp3（+）IL-10（+）调节性T细胞。最后，从OVA-IL-10-DC注射的小鼠的CD4（+）纵隔淋巴结T细胞的过继转移保护了OVA激发后，OVA敏感的受体免受气道嗜酸性粒细胞增多。我们的研究描述了在气道过敏中诱导持久的Ag特异性耐受的有前途的策略。

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