Epicutaneous (EC) sensitization with protein allergens is the most important sensitization route for atopic dermatitis. Plasmacytoid dendritic cells (pDCs) are characterized by massive secretion of interferon-α (IFNα). B6 mice are T helper type 1 (Th1)-prone and are representative of non-atopic humans, whereas BALB/c mice are Th2-prone and are representative of atopic humans. Here, we show that naïve BALB/c mice contain a greater number of nonactivated pDCs in peripheral lymph nodes (LNs) than do naïve B6 mice. Naïve BALB/c mice also have more of the CD8α- subset in LNs than naïve B6 mice. Moreover, in vivo depletion of pDCs during EC sensitization results in enhanced Th2 responses in BALB/c mice, but not in B6 mice. Mechanistically, when BALB/c mice undergo EC sensitization, there is an increase in pDCs entering draining LNs. These cells exhibit modest activation including comparable costimulation expression but increased cytokine expression compared with those of naïve mice. In vivo depletion of pDCs during EC sensitization significantly increases the activation of dermal dendritic cells (dDCs) suggesting a regulatory effect on these cells. To this end, a suppressive effect of pDCs on conventional dendritic cells was also demonstrated in vitro. Further, in vivo blockade of IFNα by an anti-IFNAR antibody (Ab) or in vivo reduction of IFNα production of pDCs by anti-siglec-H Ab both resulted in enhanced activation of dDCs. Collectively, our results demonstrate that pDCs suppress Th2 responses induced by EC sensitization via IFNα-mediated regulation of dDCs.

中文翻译：

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浆细胞样树突状细胞抑制由表皮致敏作用诱导的Th2反应。

蛋白过敏原的表皮（EC）致敏是特应性皮炎最重要的致敏途径。浆细胞样树突状细胞（pDC）的特征是大量分泌干扰素-α（IFNα）。B6小鼠易患T辅助1型（Th1），并代表非特应性人类，而BALB / c小鼠易受T2辅助，并代表特应性人类。在这里，我们表明，与单纯的B6小鼠相比，幼稚的BALB / c小鼠在外周淋巴结（LNs）中包含的非激活pDC数量更多。幼稚的BALB / c小鼠也比幼稚的B6小鼠具有更多的LNsCD8α-亚型。此外，在EC致敏过程中pDC的体内耗竭导致BALB / c小鼠的Th2反应增强，而B6小鼠却没有。从机理上讲，当BALB / c小鼠经历EC致敏时，进入排泄LN的pDC增加。这些细胞表现出适度的激活，包括可比的共刺激表达，但与幼稚小鼠相比，细胞因子表达增加。EC致敏过程中pDC的体内耗竭显着增加了皮肤树突状细胞（dDC）的激活，表明对这些细胞具有调节作用。为此，在体外也证明了pDC对常规树突细胞的抑制作用。此外，抗-IFNAR抗体（Ab）的体内对IFNα的阻断或抗-siglec-H Ab的体内pDC的IFNα产生的减少均导致dDC的活化增强。总体而言，我们的结果表明pDC通过IFNα介导的dDC调节抑制EC致敏作用诱导的Th2反应。