Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production.
Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production.
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DOI：
10.1017/s0007114514001998
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发表时间：
2014-12-14
影响因子：
3.6
通讯作者：
Honkanen, Jarno
中科院分区：
文献类型：
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作者：
Paasela, Monika;Kolho, Kaija-Leena;Vaarala, Outi;Honkanen, Jarno
我们对乳糖作为免疫调节分子的兴趣来自于显示乳糖与半乳糖凝集素-9结合的研究，半乳糖凝集素-9已被证明在免疫系统中具有各种调节功能，包括调节T细胞应答。辅助性T细胞（Th）1和Th 17型免疫应答的调节受损以及调节性T细胞（Treg）功能障碍与许多人类免疫介导的疾病有关。在本研究中，我们研究了乳糖对免疫调节的影响，使用人外周血单核细胞（PBMC）来源的Treg和效应T细胞（Teff）从20个健康成人获得的共培养物。通过免疫磁性分离从PBMC中分离Treg，即CD 4 + CD 25 + CD 127-。将去除CD 25+细胞的CD 4 + CD 127 −细胞部分用作Teff。Treg和Teff以1：5的比例被激活，并使用蛋白质的ELISA和mRNA的定量RT-PCR分析乳糖对干扰素-γ（IFN-γ）和IL-17分泌的影响。Treg下调IFN-γ的分泌，（8.8 - 3.9 ng/ml，n 20，P= 0.003）和IL-17（0.83 - 0.64 ng/ml，n = 15，P= 0.04），而在乳糖存在下，IFN-γ和IL-17的分泌水平仍然很高，没有观察到下调（16·4 v.3·99 ng/ml，n 20，P< 0·0001; 0·74 v.0·64 ng/ml，n 15，P= 0·005）。我们发现，乳糖抑制人Treg介导的抑制Th 1和Th 17免疫反应在体外。
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.