Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3+ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models.
Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3+ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models.
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DOI：
10.1371/journal.pone.0168919
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Suen JL
中科院分区：
文献类型：
--
作者：
Wong TH;Chen HA;Gau RJ;Yen JH;Suen JL
树突状细胞（Dendritic cells，DC）是介导免疫应答向炎症或抗炎状态转变的关键细胞。血红素氧合酶-1（HO-1）因其抗氧化应激和炎症的细胞保护作用而闻名，提示其在变应性肺部炎症中的免疫调节作用。HO-1参与影响DC成熟;然而，其在DC介导的T细胞分化中的作用尚不清楚。在这项研究中，我们证明了HO-1表达骨髓来源的树突状细胞（BM-DCs）显示耐受性表型，包括其抵抗脂多糖（LPS）诱导的成熟，高水平的IL-10表达，和低T细胞刺激活性。此外，HO-1表达的DC能够在体外和体内诱导抗原特异性Foxp 3+调节性T细胞（Treg）分化。此外，HO-1表达的DC调制的严重程度，肺部炎症反应在两个小鼠模型的气道炎症。本研究为支持HO-1表达的DC在耐受诱导中的作用以及作为过敏性哮喘以及其他炎症性疾病的潜在治疗靶点提供了证据。
Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3+ regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.
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