Plexin-B2 and Plexin-D1 in dendritic cells: Expression and IL-12/IL-23p40 production

Eda K. Holl, Kelly E. Roney, Irving C. Allen, Erin Steinbach, Janelle C. Arthur, Adam Buntzman, Scott Plevy, Jeffrey Frelinger, Jenny P.Y. Ting

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Article numbere43333
JournalPloS one
Volume7
Issue number8
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Holl, E. K., Roney, K. E., Allen, I. C., Steinbach, E., Arthur, J. C., Buntzman, A., Plevy, S., Frelinger, J., & Ting, J. P. Y. (2012). Plexin-B2 and Plexin-D1 in dendritic cells: Expression and IL-12/IL-23p40 production. PloS one, 7(8), [e43333]. https://doi.org/10.1371/journal.pone.0043333