Increased expression of mGITRL on D2SC/1 cells by particulate β-glucan impairs the suppressive effect of CD4+CD25+ regulatory T cells and enhances the effector T cell proliferation

Cell Immunol. 2011;270(2):183-7. doi: 10.1016/j.cellimm.2011.05.003. Epub 2011 May 10.

Abstract

β-Glucans have been shown to enhance immune responses for centuries, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Dectin-1, the C-type lectin receptor for β-glucan, is expressed abundantly on dendritic cells (DCs). Activation of DCs via Dectin-1 can lead to the maturation of DC, inducing both innate and adaptive immune responses against tumor development and microbial infection. In this study, we found that particulate yeast-derived β-glucans could induce the maturation of murine dendritic cell line D2SC/1 cells and increase the expression of mGITRL on D2SC/1 cells via Dectin-1/Syk pathway in a dose dependent manner. Furthermore, we demonstrated that the increased mGITRL on D2SC/1 cells could impair the suppressive activity of CD4(+)CD25(+) regulatory T cells (Tregs) and enhance the proliferation of CD4(+)CD25(-) effector T cells (Teffs). These findings suggest that particulate β-glucan can be used as immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate immune suppressive activity, leading to a more efficient defense mechanism against tumor development or infectious diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Gene Expression / drug effects
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Necrosis Factors / genetics*
  • beta-Glucans / administration & dosage
  • beta-Glucans / immunology*
  • beta-Glucans / pharmacology*

Substances

  • Immunologic Factors
  • RNA, Messenger
  • Tnfsf18 protein, mouse
  • Tumor Necrosis Factors
  • beta-Glucans