Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
PLoS One. 2012;7(8):e43333. doi: 10.1371/journal.pone.0043333. Epub 2012 Aug 15.
Plexins are a family of genes (A,B,C, and D) that are expressed in many organ systems. Plexins expressed in the immune system have been implicated in cell movement and cell-cell interaction during the course of an immune response. In this study, the expression pattern of Plexin-B2 and Plexin-D1 in dendritic cells (DCs), which are central in immune activation, was investigated. Plexin-B2 and Plexin-D1 are reciprocally expressed in myeloid and plasmacytoid DC populations. Plasmacytoid DCs have high Plexin-B2 but low Plexin-D1, while the opposite is true of myeloid DCs. Expression of Plexin-B2 and Plexin-D1 is modulated upon activation of DCs by TLR ligands, TNFα, and anti-CD40, again in a reciprocal fashion. Semaphorin3E, a ligand for Plexin-D1 and Plexin-B2, is expressed by T cells, and interestingly, is dramatically higher on Th2 cells and on DCs. The expression of Plexins and their ligands on DCs and T cells suggest functional relevance. To explore this, we utilized chimeric mice lacking Plxnb2 or Plxnd1. Absence of Plexin-B2 and Plexin-D1 on DCs did not affect the ability of these cells to upregulate costimulatory molecules or the ability of these cells to activate antigen specific T cells. Additionally, Plexin-B2 and Plexin-D1 were dispensable for chemokine-directed in-vitro migration of DCs towards key DC chemokines, CXCL12 and CCL19. However, the absence of either Plexin-B2 or Plexin-D1 on DCs leads to constitutive expression of IL-12/IL-23p40. This is the first report to show an association between Plexin-B2 and Plexin-D1 with the negative regulation of IL-12/IL-23p40 in DCs. This work also shows the presence of Plexin-B2 and Plexin-D1 on mouse DC subpopulations, and indicates that these two proteins play a role in IL-12/IL-23p40 production that is likely to impact the immune response.
丛蛋白是一个基因家族（A、B、C 和 D），在许多器官系统中表达。免疫系统中表达的丛蛋白已被牵连到免疫反应过程中的细胞运动和细胞-细胞相互作用中。在这项研究中，研究了在免疫激活中起核心作用的树突状细胞（DC）中丛蛋白-B2 和丛蛋白-D1 的表达模式。在髓样和浆细胞样 DC 群体中，丛蛋白-B2 和丛蛋白-D1 呈相互表达。浆细胞样 DC 具有高的丛蛋白-B2 但低的丛蛋白-D1，而髓样 DC 则相反。当 DC 被 TLR 配体、TNFα 和抗 CD40 激活时，丛蛋白-B2 和丛蛋白-D1 的表达也会以相互的方式被调节。神经鞘氨醇 3E 是丛蛋白-D1 和丛蛋白-B2 的配体，由 T 细胞表达，有趣的是，它在 Th2 细胞和 DC 上的表达显著更高。DC 和 T 细胞上丛蛋白及其配体的表达表明其具有功能相关性。为了探索这一点，我们利用缺乏 Plxnb2 或 Plxnd1 的嵌合小鼠。DC 上缺乏丛蛋白-B2 和丛蛋白-D1 不会影响这些细胞上调共刺激分子的能力，也不会影响这些细胞激活抗原特异性 T 细胞的能力。此外，在趋化因子导向的 DC 向关键 DC 趋化因子 CXCL12 和 CCL19 的体外迁移中，丛蛋白-B2 和丛蛋白-D1 也是可有可无的。然而，无论是 DC 上缺乏丛蛋白-B2 还是丛蛋白-D1，都会导致 IL-12/IL-23p40 的组成型表达。这是第一个报道表明丛蛋白-B2 和丛蛋白-D1 与 DC 中 IL-12/IL-23p40 的负调控有关的报告。这项工作还表明，在小鼠 DC 亚群中存在丛蛋白-B2 和丛蛋白-D1，并表明这两种蛋白在 IL-12/IL-23p40 产生中发挥作用，这可能会影响免疫反应。
