T cells are the main population in mouse breast milk and express similar profiles of tight junction proteins as those in mammary alveolar epithelial cells
T cells are the main population in mouse breast milk and express similar profiles of tight junction proteins as those in mammary alveolar epithelial cells
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DOI：
10.1016/j.jri.2020.103137
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发表时间：
2020-08-01
影响因子：
3.4
通讯作者：
Tomura, Michio
中科院分区：
文献类型：
--
作者：
Ikebuchi, Ryoyo;Fujimoto, Maika;Tomura, Michio
免疫细胞存在于多种哺乳动物的母乳中；然而，它们的免疫功能和向牛奶的迁移机制仍然未知。一些研究人员假设乳汁白细胞起源于乳腺 (MG)，并通过细胞旁途径迁移，但乳腺泡上皮细胞在哺乳期间通过紧密连接 (TJ) 等屏障结构严格调节乳汁成分的细胞旁运动。为了研究这种差异，我们比较了小鼠 MG 和牛奶中的白细胞群，并探索了 MG 白细胞中的 TJ 蛋白表达谱。乳汁白细胞的主要亚群是表现出记忆表型的CD8(+)和CD4(+)T细胞。牛奶中的髓系细胞、B 细胞和树突状细胞的比例显着低于 MG 中的比例。与哺乳期小鼠 MG 中的骨髓细胞和 B 细胞相比，CD8+ T 细胞以更高水平表达编码 TJ 蛋白claudin-3、-7、-12 和 ZO-1 的基因。 MG 中的肺泡上皮细胞表达claudin-3、-4 和-7。 FTY720（一种 1-磷酸鞘氨醇受体 1 的抑制性激动剂，可稳定 TJ 通透性）的给药可增加乳汁中骨髓细胞的比例。 MG 和乳汁中的不同白细胞群表明细胞向乳汁迁移的主动和选择性机制。 MG 的肺泡上皮细胞中的 TJ 形成成分和 MG 的白细胞中的 TJ 蛋白表达谱似乎都能调节乳汁白细胞群。 T 细胞是小鼠母乳中的主要群体，表达与乳腺肺泡上皮细胞相似的 TJ 蛋白谱。
Immune cells are present in the breast milk of several mammalian species; however, their immunological function and transmigration mechanisms to milk remain unknown. Some researchers hypothesize that milk leukocytes have a mammary gland (MG) origin and transmigrate thorough the paracellular pathway, but mammary alveolar epithelial cells strictly regulate the paracellular movement of milk components during lactation via barrier structures, such as tight junctions (TJs). To investigate this discrepancy, we compared leukocyte populations in mouse MG and milk and explored TJ protein expression profiles in MG leukocytes. The main subsets of milk leukocytes were CD8(+) and CD4(+) T cells displaying the memory phenotype. The proportions of myeloid, B, and dendritic cells were significantly lower in milk than in the MG. CD8(+) T cells expressed genes encoding the TJ proteins claudin-3, -7, -12, and ZO-1 at higher levels when compared with myeloid and B cells in the MG among lactating mice. Alveolar epithelial cells in the MG expressed claudin-3, -4, and -7. Administration of FTY720, an inhibitory agonist of sphingosine 1-phosphate receptor 1 that stabilizes TJ permeability, increased the myeloid cell proportion in milk. Different leukocyte populations in the MG and milk suggest active and selective mechanisms of cell transmigration to milk. Both TJ-forming components in alveolar epithelial cells from the MG and TJ protein expression profiles in leukocytes from the MG appear to regulate milk leukocyte populations. T cells are the main population in mouse breast milk and express similar profiles of TJ proteins as those in mammary alveolar epithelial cells.