Chunder Rittika, Weier Alicia, An Young, Zoons Angelika, Hintze Maik, Kuerten Stefanie
Institute of Neuroanatomy, Medical Faculty, University of Bonn and University Hospital Bonn, Bonn, Germany.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
Neurogastroenterol Motil. 2025 Nov;37(11):e70142. doi: 10.1111/nmo.70142. Epub 2025 Aug 14.
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with evidence of autoimmune attack also on the enteric nervous system (ENS). The role of different dietary antigens, including bovine milk proteins, in the exacerbation of MS symptoms has previously been discussed.
In a mouse model of neuroinflammation, we characterized the extent of ENS pathology in animals that were immunized with different bovine milk antigens using electron microscopy, immunohistochemistry, molecular biology, and cell culture as key methods.
Our data demonstrate that immunization of mice with bovine milk casein resulted in ENS pathology, which is in line with our previous findings where casein-immunized mice also exhibited demyelination in the CNS. Furthermore, development of ENS pathology was most likely due to a combination of cellular and humoral factors, as confirmed by our observation of CD3 T cell infiltration in the tunica muscularis and binding of serum antibodies from casein-immunized mice to glial cells in the myenteric plexus.
The findings presented in this paper reflect that exposure to bovine casein can result in axolysis in the myenteric plexus possibly as a result of molecular mimicry and antibody cross-reactivity between casein and antigen(s) expressed by the ENS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的免疫介导性脱髓鞘疾病，有证据表明自身免疫攻击也发生在肠神经系统（ENS）。此前已讨论过包括牛乳蛋白在内的不同饮食抗原在MS症状加重中的作用。
在一种神经炎症小鼠模型中，我们以电子显微镜、免疫组织化学、分子生物学和细胞培养为关键方法，对用不同牛乳抗原免疫的动物的ENS病理学程度进行了表征。
我们的数据表明，用牛乳酪蛋白免疫小鼠会导致ENS病理学变化，这与我们之前的研究结果一致，即酪蛋白免疫的小鼠在CNS中也表现出脱髓鞘。此外，ENS病理学的发展很可能是细胞和体液因素共同作用的结果，我们观察到肌层中有CD3 T细胞浸润以及酪蛋白免疫小鼠的血清抗体与肌间神经丛中的神经胶质细胞结合，证实了这一点。
本文的研究结果表明，接触牛乳酪蛋白可能会导致肌间神经丛中的轴突溶解，这可能是由于酪蛋白与ENS表达的抗原之间的分子模拟和抗体交叉反应所致。
