Laboratorio de Inmunidad de Mucosas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Salvador Díaz Mirón y Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, México City 11340, Mexico.
Laboratorio de Investigación Biomédica del Hospital Regional de Alta Especialidad de Oaxaca, San Bartolo Coyotepec 71256, Mexico.
Nutrients. 2021 Aug 19;13(8):2852. doi: 10.3390/nu13082852.
Bovine lactoferrin (bLf), a component of milk and a dietary supplement, modulates intestinal immunity at effector and inductor sites. Considering the regional difference in intestinal compartments and the dynamics of local cytokine-producing cells in the gut across time, the aim of this work was to characterize the effects of bLf on the proximal small intestine in a BALB/c murine model of oral administration. Male BALB/c mice were treated with oral bLf vs. saline control as mock by buccal deposition for 28 days. Intestinal secretions were obtained at different time points and cells were isolated from Peyer's patches (PP) and lamina propria (LP) of the proximal small intestine as representative inductor and effector sites, respectively. Total and specific anti-bLF IgA and IgM were determined by enzyme-immuno assay; the percentages of IgA and IgM plasma cells (PC) and cytokine-producing CD4 T cells of PP and LP were analyzed by flow cytometry. We found that total and bLf-specific IgA and IgM levels were increased in the intestinal secretions of the bLf group in comparison to mock group and day 0. LP IgA PC and IgM PC presented an initial elevation on day 7 and day 21, respectively, followed by a decrease on day 28 in comparison to mock. Higher percentages of CD4 T cells in LP were found in the bLf group. Cytokines-producing CD4 T cells populations presented a pattern of increases and decreases in the bLf group in both LP and PP. Transforming growth factor beta (TGF-β) CD4 T cells showed higher percentages after bLf administration with a marked peak at day 21 in both LP and PP in comparison to mock-treated mice. Oral bLf exhibits complex immune properties in the proximal small intestine, where temporal monitoring of the inductor and effector compartments reveals patterns of rises and falls of different cell populations. Exceptionally, TGF-β CD4 T cells show consistent higher numbers after bLf intervention across time. Our work suggests that isolated measurements do not show the complete picture of the modulatory effects of oral bLf in immunological sites as dynamic as the proximal small intestine.
牛乳铁蛋白（bLf）是牛奶的一种成分，也是一种膳食补充剂，可在效应器和诱导部位调节肠道免疫。考虑到肠道隔室的区域差异以及肠道中局部细胞因子产生细胞随时间的动态变化，本研究旨在表征 bLf 对 BALB/c 口服给药小鼠模型近端小肠的影响。雄性 BALB/c 小鼠通过口腔 bLf 处理与盐水对照（模拟）进行 28 天的口腔给药。在不同时间点获取肠道分泌物，并从派尔氏斑（PP）和近端小肠的固有层（LP）分离细胞，分别作为代表性诱导和效应部位。通过酶免疫测定法测定总 bLf 和特异性抗 bLf IgA 和 IgM；通过流式细胞术分析 PP 和 LP 中 IgA 和 IgM 浆细胞（PC）和细胞因子产生的 CD4 T 细胞的百分比。我们发现，与模拟组和第 0 天相比，bLf 组的肠道分泌物中总 bLf 和特异性 IgA 和 IgM 水平增加。LP 的 IgA PC 和 IgM PC 在第 7 天和第 21 天分别出现初始升高，然后在第 28 天与模拟组相比下降。LP 中 CD4 T 细胞的比例较高。LP 和 PP 中细胞因子产生的 CD4 T 细胞群体呈现出增加和减少的模式。转化生长因子β（TGF-β）CD4 T 细胞在 LP 和 PP 中的 bLf 给药后表现出更高的百分比，与对照处理的小鼠相比，在第 21 天达到明显高峰。口服 bLf 在近端小肠中表现出复杂的免疫特性，在诱导和效应隔室中进行时间监测可揭示不同细胞群体的升跌模式。异常的是，TGF-β CD4 T 细胞在 bLf 干预后跨时间显示出一致的更高数量。我们的工作表明，在像近端小肠这样具有动态免疫部位的情况下，孤立的测量并不能显示口服 bLf 调节作用的完整情况。
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