Abstract：
Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation is recapitulated by adoptive transfer of fetal liver precursors following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, is concomitant with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a mechanism by which early-life inflammation results in increased asthma susceptibility in the presence of hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.
摘要：
这里,我们通过对早期发育的组织内免疫细胞进行重编程,研究了产前炎症如何影响肺组织功能和免疫功能.产妇,但不是胎儿，I型干扰素介导的炎症引起接种发育中的肺的第2组先天淋巴样细胞（ILC2s）的扩增和过度激活。过度活化的ILC2s产生增加的IL-5和IL-13，并与急性Th2偏倚，减少Tregs，和持续的肺嗜酸性粒细胞增多到成年期。ILC2过度激活通过产前炎症后胎儿肝脏前体的过继转移来概括，指示胎儿祖细胞水平的发育编程。重新编程的ILC2过度激活和随后的肺免疫重塑，包括持续性嗜酸性粒细胞增多,伴随着恶化的组织病理学和增加的气道功能障碍相当于木瓜蛋白酶暴露，表明后代哮喘易感性增加。我们的数据阐明了在高活化ILC2s的存在下，早期炎症导致哮喘易感性增加的机制，这些ILC2s在围产期发育过程中驱动肺免疫的持续变化。
