p38 MAPK signaling mediates retinoic acid-induced CD103 expression in human dendritic cells.,Immunology

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p38 MAPK signaling mediates retinoic acid-induced CD103 expression in human dendritic cells.
Immunology ( IF 4.9 ) Pub Date : 2020-08-01 , DOI: 10.1111/imm.13246
Mandi M Roe ₁ , Marziah Hashimi ₁ , Steve Swain ₁ , Krista M Woo ₁ , Diane Bimczok ₁

Affiliation

Retinoic acid (RA) is an active derivative of vitamin A and a key regulator of immune cell function. In dendritic cells (DCs), RA drives the expression of CD103 (integrin α_E), a functionally relevant DC subset marker. In this study, we analyzed the cell type specificity and the molecular mechanisms involved in RA‐induced CD103 expression. We show that RA treatment caused a significant up‐regulation of CD103 in differentiated monocyte‐derived DCs and blood DCs, but not in differentiated monocyte‐derived macrophages or T cells. DC treatment with an RA receptor α (RARα) agonist led to an increase in CD103 expression similar to that in RA treatment, whereas RARA gene silencing with small interfering RNA blocked RA‐induced up‐regulation of CD103, pointing to a major role of RARα in the regulation of CD103 expression. To elucidate RA‐induced signaling downstream of RARα, we used Western blot analysis of RA‐treated DCs and showed a significant increase of p38 mitogen‐activated protein kinase (MAPK) phosphorylation. In addition, DCs cultured with RA and a p38 MAPK inhibitor had a significantly reduced expression of CD103 compared with DCs cultured with RA only, indicating that p38 MAPK is involved in CD103 regulation. In summary, these findings suggest that the RA‐induced expression of CD103 is specific to DCs, is mediated primarily through RARα and involves p38 MAPK signaling.

中文翻译：

p38 MAPK 信号在人树突细胞中介导视黄酸诱导的 CD103 表达。

视黄酸 (RA) 是维生素 A 的活性衍生物，是免疫细胞功能的关键调节剂。在树突细胞 (DC) 中，RA 驱动 CD103（整合素α _E）的表达，这是一种功能相关的 DC 子集标记物。在这项研究中，我们分析了细胞类型特异性和参与 RA 诱导的 CD103 表达的分子机制。我们表明，RA 治疗导致分化的单核细胞衍生的 DC 和血液 DC 中 CD103 的显着上调，但在分化的单核细胞衍生的巨噬细胞或 T 细胞中没有。用 RA 受体α (RAR α ) 激动剂进行DC 治疗导致 CD103 表达增加，与 RA 治疗相似，而RARA用小干扰 RNA 进行基因沉默阻断了 RA 诱导的 CD103 上调，表明 RAR α在调节 CD103 表达中起主要作用。为了阐明 RA 诱导的 RAR α下游信号传导，我们使用了 RA 处理的 DC 的蛋白质印迹分析，结果显示 p38 丝裂原活化蛋白激酶 (MAPK) 磷酸化显着增加。此外，与仅用 RA 培养的 DCs 相比，用 RA 和 p38 MAPK 抑制剂培养的 DCs 的 CD103 表达显着降低，表明 p38 MAPK 参与 CD103 调节。总之，这些发现表明 RA 诱导的 CD103 表达对 DC 具有特异性，主要通过 RAR α介导并涉及 p38 MAPK 信号传导。

更新日期：2020-08-01

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