Regulatory T Cell Depletion Abolishes the Protective Effect of Dietary Galacto-Oligosaccharides on Eosinophilic Airway Inflammation in House Dust Mite-Induced Asthma in Mice

被引:17
作者
Verheijden, Kim A. T. [1 ]
Braber, Saskia [2 ]
Leusink-Muis, Thea [1 ]
Thijssen, Suzan [1 ]
Boon, Louis [4 ]
Kraneveld, Aletta D. [1 ]
Garssen, Johan [1 ,3 ]
Folkerts, Gert [1 ]
Willemsen, Linette E. M. [1 ]
机构
[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacol, Fac Sci, Utrecht, Netherlands
[2] Univ Utrecht, Fac Vet Sci, Div Vet Pharm Pharmacol & Toxicol, Utrecht, Netherlands
[3] Nutricia Res, Immunol, Utrecht, Netherlands
[4] EPIRUS Biopharmaceut Netherlands BV, Utrecht, Netherlands
关键词
allergy; asthma; galacto-oligosaccharides; regulatory T cell; anti-CD25; ALLERGIC INFLAMMATION; BIFIDOBACTERIUM-BREVE; MURINE MODEL; CD25(+); ACTIVATION; EXPRESSION; RESPONSES; RESOLUTION; TREG;
D O I
10.3945/jn.115.224402
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Background: In a murine model for house dust mite (HDM)-induced asthma, dietary galacto-oligosaccharides have been shown to suppress allergic symptoms. Previously, CD25(+) regulatory T cells (Tregs) induced by nondigestible oligosaccharides were found to protect against allergy development. Objective: The aim of the current study was to examine the effect of anti-CD25-induced Treg depletion in a murine HDM-induced asthma model and to study the contribution of Tregs in the protective effect of dietary intervention with galacto-oligosaccharides. Methods: Male BALB/c mice (aged 6-8 wk) were intranasally sensitized and challenged with phosphate-buffered saline (PBS) or HDM. Two weeks before sensitization and throughout the whole experiment, mice were fed a control or 1% w/w galacto-oligosaccharide diet. Tregs were depleted by anti-mouse CD25 antibody (intraperitoneally injected). On day 14, T helper cell subtypes in lung and spleen were analyzed and cytokines were measured. Leukocyte subtypes were analyzed in the bronchoalveolar lavage fluid, and interleukin (IL)-33 and chemokines were measured in lung homogenate supernatants. Results: Anti-CD25 treatment depleted CD25(+) Forkhead box P3(+) Tregs in the lung and spleen of control and HDM-allergic mice (P < 0.0001) by > 70% while increasing the percentage of activated T helper cells (P < 0.05) and type 2 T helper cells (P < 0.05). This was associated with increased IL-10, IL-4, and IL-13 concentrations in supernatants of ex vivo restimulated lung cells (P < 0.01). Bronchoalveolar lavage fluid leukocyte numbers and percentages of eosinophils and lymphocytes were greater in HDM-allergic mice compared with PBS mice (P < 0.01) but remained unaffected by the anti-CD25 treatment. Galacto-oligosaccharides decreased airway eosinophilia compared with HDM-allergic mice fed the control diet (from 47.8% +/- 6.7% to 26.6% +/- 8.5%, P < 0.01). This protective effect was lost in anti-CD25-treated mice (P < 0.05). In lung homogenates of HDM-allergic mice, IL-33 was increased compared with PBS mice (from 2.8 +/- 0.3 to 5.4 +/- 0.6 ng protein/mg, P < 0.01). Galacto-oligosaccharides abrogated the increase in IL-33 compared with HDM-allergic mice fed the control diet (3.0 +/- 0.6 ng protein/mg, P < 0.05), which was abolished by the anti-CD25 treatment (P < 0.01). Conclusions: Treg depletion enhances pulmonary type 2 T helper cell frequency and cytokine release in HDM-induced asthma in mice. Galacto-oligosaccharides decreased airway eosinophilia and IL-33 concentrations in the lung, which was abrogated by Treg depletion. This indicates that galacto-oligosaccharides have a beneficial effect in the prevention of HDM-induced allergic asthma by supporting pulmonary Treg function.
引用
收藏
页码:831 / 837
页数:7
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