Department of Immunology, Lerner Research Institute, Cleveland Clinic, Ohio 44195, USA.
Am J Pathol. 2012 Sep;181(3):775-84. doi: 10.1016/j.ajpath.2012.05.025.
Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse α-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with α-lactalbumin showed extensive T-cell-mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with α-lactalbumin had no effect on fertility and birth numbers, pups nursed by α-lactalbumin-immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based "failure-to-thrive" issues, particularly regarding the long-term implications of postnatal nutritional deprivation.
乳腺炎是哺乳期妇女面临的一个严重的临床问题，可能导致严重的疼痛和突然中断母乳喂养，从而使婴儿面临长期健康风险。许多乳腺炎病例没有已知的感染源，可能根本上是由于乳腺的自身免疫性炎症引起的。在这里，我们建立了一种自身免疫性乳腺炎的小鼠模型，并详细描述了其导致的乳房衰竭和哺乳不足的表型。为了产生乳腺特异性自身免疫，我们用重组鼠α-乳白蛋白免疫 SWXJ 小鼠，α-乳白蛋白是一种与泌乳相关的、乳腺特异性的分化蛋白，对乳糖的产生至关重要。用α-乳白蛋白免疫的小鼠在哺乳期正常乳腺实质中表现出广泛的 T 细胞介导的炎症，但在非哺乳期正常乳腺实质中则没有。这种靶向自身免疫攻击导致了以哺乳不足和哺育后代能力下降为特征的乳房衰竭。尽管用α-乳白蛋白免疫对生育力和产仔数没有影响，但用α-乳白蛋白免疫的小鼠哺乳的幼崽生长明显受到干扰，常伴有类 kwashiorkor 的营养异常，包括脱发、肝毒性和发育不良。这种自身免疫性乳腺衰竭的实验模型可用于预防性乳腺癌疫苗接种，并可解决哺乳期的炎症并发症。此外，该模型适用于研究基于营养的“发育不良”问题，特别是关于产后营养剥夺的长期影响。
