Plexin-B2 and Plexin-D1 in Dendritic Cells: Expression and IL-12/IL-23p40 Production

Abstract

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.

Semaphorin‐3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C+ and CD4+CD25− T‐cells

“…This set of data corroborated with those obtained in our study in patients with active UC, where we demonstrated that SEMA3E was negatively correlated with cells expressing CD11C and maturation markers IL12/IL23p19 . These findings are in agreement with previous data showing that a deficiency in SEMA3E receptors (plexin‐D1 and plexin‐B2) is associated with a negative regulation of IL‐12/IL‐23p40 in CD11C‐dendritic cells (DC; Holl et al, ). Moreover, Movassagh, Shan, Mohammed, et al () depicted that the deletion of Sema3e can enhance the recruitment of pulmonary DC and can result in a worsening of the allergic airway inflammation, associated with an increase in T‐cell activation.…”

Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation

“…However, later we and others have demonstrated Plexin B1 and/or D1 expression in the immune system, particularly on DC (10,20), T cells (21) and Treg cells (our unpublished observations).…”

The role and mechanism-of-action of Sema3E and Plexin-D1 in vascular and neural development

“…It has recently been revealed that Plexin-D1 is also expressed during B lymphocyte activation and enables these cells to respond to germinal center chemokines such as CXCL12, CXCL13 and CCL19 from the germinal center [29]. In dendritic cells, Plexin-D1 is a negative regulator of IL-12/IL-23p40 response [30]. …”