IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring.
IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring.
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DOI：
10.1186/1476-7961-8-9
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发表时间：
2010-07-13
期刊：
影响因子：
--
通讯作者：
Puddington L
中科院分区：
文献类型：
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作者：
Matson AP;Thrall RS;Rafti E;Lingenheld EG;Puddington L
母乳喂养婴儿患过敏性疾病风险降低的机制尚未完全清楚。使用一个已建立的小鼠哮喘模型，我们先前证明了从过敏性母亲传递给母乳喂养后代的对过敏性气道疾病的抵抗需要母体B细胞衍生因子。本研究的目的是探讨后代新生儿Fc受体的作用，IgG摄取肠上皮细胞（FcRn）在这母乳转移保护过敏。在C57 BL/6雌性小鼠妊娠期间诱导过敏性气道疾病。这些过敏性母鼠培育与C57 BL/6 J-FcRn-/-雄性小鼠交配的FcRn+/-雌性小鼠所生的哺乳期幼稚FcRn +/-或FcRn-/-后代。在缺乏FcRn的后代中，我们预计全身过敏原特异性IgG 1水平会降低，这是新生儿胃肠道内腔对母体IgG吸收减少的结果。使用该模型，我们能够研究母乳IgG如何影响后代对过敏性致敏的反应。在断奶FcRn充足或缺乏的小鼠中测定从过敏性养母的母乳中吸收的母体抗体水平。母体将过敏原特异性IgG 1传递给母乳喂养的FcRn-/-后代的水平比在FcRn+/-或FcRn+/+小鼠中观察到的水平低103-104。断奶后5周，当后代8周龄时，对小鼠进行致敏和激发，以评估其发生过敏性气道疾病的易感性。由过敏性母亲喂养的FcRn充足小鼠的新生儿中，疾病参数（血清中的过敏原特异性IgE、气道和肺中的嗜酸性粒细胞炎症）降低表明了保护作用。相比之下，由相同母亲母乳喂养的FcRn缺陷小鼠获得有限的（如果有的话）保护免于过敏原特异性IgE和相关病理的发展。FcRn表达是决定过敏母亲母乳喂养的后代获得足以抑制该模型中过敏性致敏的全身性过敏原特异性IgG 1水平的主要因素。
The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors. The aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy. Allergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/- or FcRn-/- progeny born to FcRn+/- females that were mated to C57BL/6J-FcRn-/- male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization. Levels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology. FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.