Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production

Br J Nutr. 2014 Dec 14;112(11):1819-25. doi: 10.1017/S0007114514001998. Epub 2014 Oct 21.

Abstract

Our interest in lactose as an immunomodulatory molecule results from studies showing that lactose binds to galectin-9, which has been shown to have various regulatory functions in the immune system including regulation of T-cell responses. Impaired regulation of T helper (Th)1 and Th17 type immune responses and dysfunction of regulatory T cells (Treg) have been implicated in many human immune-mediated diseases. In the present study, we investigated the effects of lactose on immune regulation using co-cultures of human peripheral blood mononuclear cell (PBMC)-derived Treg and effector T cells (Teff) obtained from twenty healthy adults. Treg, i.e. CD4+CD25+CD127-, were isolated from PBMC by immunomagnetic separation. The fraction of CD4+CD127- cells that was depleted of CD25+ cells was used as Teff. Treg and Teff at a ratio 1:5 were activated and the effects of lactose on the secretion of interferon-γ (IFN-γ) and IL-17 were analysed using ELISA for protein and quantitative RT-PCR for mRNA. Treg down-regulated the secretion of both IFN-γ (8.8-3.9 ng/ml, n 20, P= 0.003) and IL-17 (0.83-0.64 ng/ml, n 15, P= 0.04) in co-cultures, while in the presence of lactose the levels of secreted IFN-γ and IL-17 remained high and no down-regulation was observed (16.4 v. 3.99 ng/ml, n 20, P< 0.0001, and 0.74 v. 0.64 ng/ml, n 15, P= 0.005, respectively). We showed that lactose inhibits human Treg-mediated suppression of Th1 and Th17 immune responses in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dietary Carbohydrates / pharmacology
  • Galectins / biosynthesis
  • Gene Expression / drug effects
  • Humans
  • Immunologic Factors / pharmacology
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Lactose / pharmacology*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology

Substances

  • Dietary Carbohydrates
  • Galectins
  • Immunologic Factors
  • Interleukin-17
  • LGALS9 protein, human
  • Interferon-gamma
  • Lactose