Sterigmatocystin alters the number of FoxP3+ regulatory T cells and plasmacytoid dendritic cells in BALB/c mice

Food Chem Toxicol. 2012 Jun;50(6):1920-6. doi: 10.1016/j.fct.2012.03.005. Epub 2012 Mar 10.

Abstract

Sterigmatocystin (ST), a mycotoxin with mutagenic, cytotoxic and carcinogenic properties, is commonly found as the contaminant in grains and animal feeds. Of particular interest is the capacity of ST to alter normal immune function when presented in foods. As part of an on-going investigation of ST toxicological effects, we attempt to explore the short-term immunotoxic effects of ST, specifically on FoxP3(+) regulatory T cells (FoxP3(+) Tregs) and plasmacytoid dendritic cells (pDCs), by observing changes in number/expression of FoxP3(+) Tregs, pDCs and CD4(+), CD8(+) T cells in BALB/c mice 24h after a single intraperitoneal administration of ST at different dosages (3, 30, 300 and 3000 μg/kg body weight). The present study showed that 24h after ST treatment, the proportion of CD8(+) T cells was decreased in the thymus in ST 3 μg/kg group, while that of CD4(+) and CD8(+) T cells was increased in the spleen in two treatment groups (3 and 30 μg/kg). The proportion of FoxP3(+) Tregs and FoxP3 expressions were all significantly increased in mPBMCs, the thymus and the spleen. It is noteworthy that the population of pDCs significantly decreased in the thymus as we expected but increased in the spleen as compared with control, which we suspect is resulted from a temporary immune response triggered by the ST inhibition. We believe that ST may exert its immunotoxic effects by stimulating Treg, but inhibiting pDCs in the long-term to contribute its carcinogenic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • Carcinogens / pharmacology*
  • Cell Count
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Dendritic Cells / drug effects*
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / physiology*
  • Immunohistochemistry
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Polymerase Chain Reaction
  • RNA / genetics
  • RNA / isolation & purification
  • Spleen / cytology
  • Sterigmatocystin / pharmacology*
  • T-Lymphocytes, Regulatory / drug effects*
  • Thymus Gland / cytology

Substances

  • Carcinogens
  • DNA, Complementary
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-3 Receptor alpha Subunit
  • Sterigmatocystin
  • RNA