Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, Netherlands.
FrieslandCampina, Amersfoort, Netherlands.
Front Immunol. 2018 Feb 12;9:143. doi: 10.3389/fimmu.2018.00143. eCollection 2018.
During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms which cow's milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.
在过去的几十年中，世界见证了过敏患病率的急剧增加。流行病学证据表明，在农场长大是一种保护因素，这部分可以通过食用生牛乳来解释。事实上，最近的研究表明，在生命早期食用生牛乳与哮喘、花粉热和鼻炎呈负相关。最近还发现了生牛乳消费与呼吸道感染之间的类似关联。与这些发现一致，对婴儿进行的含有乳成分（如乳铁蛋白、乳脂肪球膜和初乳 IgG）的对照研究表明，可减少呼吸道感染。然而，由于伦理原因，在婴儿中进行生牛乳对照研究是不可能的，因此目前缺乏正式证据。由于儿童的病毒呼吸道感染和过敏原暴露可能与哮喘的发展有关，因此研究牛乳成分是否可以调节呼吸道中的人体免疫功能以及哪种机制是很有意义的。吸入性过敏原和病毒会在上呼吸道的鼻腔和口腔淋巴组织中引发局部免疫反应。生牛乳中的成分能够促进局部微环境的形成，从而改变黏膜免疫反应并加强上皮屏障。此外，在鼻腔中暴露于过敏原和病毒后，这些过敏原和病毒可在吞咽后进入胃肠道，从而在胃肠道中发挥作用，引发肠道中的免疫反应。然而，这些与肠道中的牛乳成分接触的免疫细胞必须再循环到血液中，并归巢到（上、下）呼吸道，以局部调节免疫反应。淋巴细胞上组织归巢相关标志物 α4β7 和 CCR9 或 CCR10 的表达可分别受到维生素 A 和维生素 D3 的影响。由于这两种维生素都存在于牛奶中，我们推测生牛奶可能会影响淋巴细胞向呼吸道的归巢。本文综述了牛乳或其成分影响肠道和上呼吸道免疫功能的潜在机制。揭示这些复杂的机制可能有助于开发新型饮食方法来预防过敏和哮喘。
