title: Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production.
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.
authors.affiliation: Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare,Haartmaninkatu 8,FI-00290Helsinki,Finland.
authors.forename: Monika
authors.initials: M
authors.lastname: Paasela
authors.affiliation: Children's Hospital, University of Helsinki,Helsinki,Finland.
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.affiliation: Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare,Haartmaninkatu 8,FI-00290Helsinki,Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.affiliation: Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare,Haartmaninkatu 8,FI-00290Helsinki,Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Honkanen
mesh_terms: D000328:Adult; D004040:Dietary Carbohydrates / Q000494:pharmacology; D037161:Galectins / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D007785:Lactose / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D004040:Dietary Carbohydrates; D037161:Galectins; D007155:Immunologic Factors; D020381:Interleukin-17; C105032:LGALS9 protein, human; D007371:Interferon-gamma; D007785:Lactose