嗜酸性粒细胞在生殖过程中驱动肠道重塑和先天防御
嗜酸性粒细胞在生殖过程中驱动肠道重塑和先天防御
作者： 小柯机器人 发布时间：2026/5/14 17:29:07
本期文章：《自然》：Online/在线发表
美国普林斯顿大学Ai Ing Lim团队的最新研究揭示了嗜酸性粒细胞在生殖过程中驱动肠道重塑和先天防御。这一研究成果于2026年5月13日发表在国际顶尖学术期刊《自然》上。
在这里，课题组人员报道了一种以前未被认识到的嗜酸性粒细胞（一种通常与过敏和蠕虫感染相关的粒细胞）在生殖过程中重塑肠道屏障的作用。在没有感染或炎症的情况下，嗜酸性粒细胞在小肠中积聚，从怀孕开始到哺乳期达到高峰。利用遗传和药理学干扰、类器官培养、单细胞和空间转录组学，研究团队发现嗜酸性粒细胞以干细胞固有的方式促进杯状细胞分化，从而导致多泡细胞的产生增加。这种重塑在哺乳期间达到高潮，并限制病原体的进入和传播，赋予广泛的先天保护，防止肠道细菌感染。
此外，在小鼠中，肠道重塑和先天防御在哺乳停止后持续数周。他们的研究结果表明，尽管在繁殖过程中普遍存在系统性免疫调节的趋势，但母体肠道会经历重塑以加强先天防御，这种机制可能已经进化到在富含病原体的环境中保护母亲和后代。更广泛地说，课题组建立了一个研究整个生殖周期中组织特异性免疫适应的框架，并强调组织可以在生理生殖后保持变化，对宿主防御和妇女健康具有持久的影响。
研究人员表示，哺乳动物的繁殖需要大量的免疫适应来保证繁殖的成功，并最终塑造一个物种的进化轨迹。妊娠期全身和胎盘免疫向耐受转变；然而，从怀孕到产后哺乳期，母体免疫是如何在屏障组织中进行适应的，屏障组织是经常感染和炎症的部位。
附：英文原文
Title: Eosinophils drive intestinal remodelling and innate defence in reproduction
Author: Huang, Chenyan, Sun, Amanda, Reyes, Jojo, Ribeiro de Souza, Jessica, Cafiero, Thomas R., Antunes Fernandes, Krist H., Oliveira, Fabricio Marcus Silva, Qiao, Yujie, Gazzinelli-Guimaraes, Pedro, Pritykin, Yuri, Lim, Ai Ing
Issue&Volume: 2026-05-13
Abstract: Mammalian reproduction requires substantial immune adaptations to safeguard reproductive success and to ultimately shape the evolutionary trajectories of a species. Systemic and placental immunity shift towards tolerance during pregnancy1,2; however, how maternal immunity adapts in barrier tissues—which are sites of frequent infection and inflammation—from pregnancy until the postpartum lactation period remains poorly understood. Here we report a previously unrecognized role for eosinophils, a type of granulocyte typically associated with allergies and helminth infections3,4, in remodelling the intestinal barrier during reproduction. Beginning in pregnancy and peaking during lactation, eosinophils accumulate in the small intestine in the absence of infection or inflammation. Using genetic and pharmacological perturbations, organoid cultures and single-cell and spatial transcriptomics, we show that eosinophils promote goblet cell differentiation in a stem-cell-intrinsic manner that leads to increased mucus production. This remodelling culminates during lactation and limits pathogen entry and dissemination to confer broad innate protection against enteric bacterial infections. Moreover, in mice, intestinal remodelling and innate defence persist weeks after lactation cessation. Our findings demonstrate that despite a general trend towards systemic immune modulation during reproduction, the maternal intestine undergoes remodelling to strengthen innate defence, a mechanism that may have evolved to protect mothers and offspring in pathogen-rich environments. More broadly, we establish a framework for studying tissue-specific immune adaptation across the reproductive cycle and highlight that tissues can retain changes following physiological reproduction, with lasting implications for host defence and women’s health.
DOI: 10.1038/s41586-026-10531-6
Source: https://www.nature.com/articles/s41586-026-10531-6