Synchronization of mothers and offspring promotes tolerance and limits allergy
Synchronization of mothers and offspring promotes tolerance and limits allergy
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DOI：
10.1172/jci.insight.137943
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发表时间：
2020-08-06
期刊：
影响因子：
8
通讯作者：
Newberry, Rodney D.
中科院分区：
文献类型：
--
作者：
Knoop, Kathryn A.;McDonald, Keely G.;Newberry, Rodney D.
过敏性疾病的特征是对环境物质的Th2免疫反应，在西方社会的儿童中越来越常见。多项研究表明，母乳喂养、早期补充食物过敏原以及在生命第一年避免使用抗生素可以减少高危儿童的过敏结果。为什么这些做法的益处仅限于早期生活，人们在很大程度上不得而知。我们确定了断奶前的间隔，在此期间，日粮抗原被结肠免疫系统同化。这一间隔是由母体通过母乳的时间变化控制的，与幼稚T细胞涌入结肠相吻合，随后是结肠外周衍生Tregs(PTregs)的长期种群的发展，这些pTregs可以对在此间隔期间遇到的饮食抗原具有特异性。母子代的去同步化在这些pTregs中产生了持久的缺陷，削弱了对断奶前期间和之后引入的饮食抗原的耐受性，并导致了自发的Th2反应。这些效应可以通过从断奶周围的结肠中提取的pTregs来挽救，或者通过使用断奶周围的结肠抗原呈递细胞在体外产生的Tregs来挽救。这些发现表明，母亲和她们的后代在发育平衡的免疫系统方面是同步的。
Allergic disorders, characterized by Th2 immune responses to environmental substances, are increasingly common in children in Western societies. Multiple studies indicate that breastfeeding, early complementary introduction of food allergens, and antibiotic avoidance in the first year of life reduces allergic outcomes in at-risk children. Why the benefit of these practices is restricted to early life is largely unknown. We identified a preweaning interval during which dietary antigens are assimilated by the colonic immune system. This interval is under maternal control via temporal changes in breast milk, coincides with an influx of naive T cells into the colon, and is followed by the development of a long-lived population of colonic peripherally derived Tregs (pTregs) that can be specific for dietary antigens encountered during this interval. Desynchronization of mothers and offspring produced durable deficits in these pTregs, impaired tolerance to dietary antigens introduced during and after this preweaning interval, and resulted in spontaneous Th2 responses. These effects could be rescued by pTregs from the periweaning colon or by Tregs generated in vitro using periweaning colonic antigen-presenting cells. These findings demonstrate that mothers and their offspring are synchronized for the development of a balanced immune system.