Eosinophils drive intestinal remodelling and innate defence in reproduction
6 affiliations
- 1Department of Molecular Biology, Princeton University, Princeton, NJ, USA
- 2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
- 3Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
- 4Department of Computer Science, Princeton University, Princeton, NJ, USA
- 5Department of Molecular Biology, Princeton University, Princeton, NJ, USA. [email protected]
- 6Howard Hughes Medical Institute, Chevy Chase, MD, USA. [email protected]
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. From pregnancy until lactation, eosinophils accumulate in the small intestine where they regulate goblet cell fate and enhance innate defences against enteric pathogens.
Related
- TLR-7 Stress Signaling in Differentiating and Mature Eosinophils Is Mediated by the Prolyl Isomerase Pin1
- Investigation of human defence responses in a virtual reality environment: an EEG study
- A Galbonolide-producing Streptomyces reconfigures the plant root microbiota by activating salicylate-dependent defence metabolism
- Multi‐Omics Analysis Uncovers the Salicylic Acid and Ethylene‐Responsive Transcription Factor‐Mediated Defence Mechanism of Panax notoginseng to Panax notoginseng Virus Y
- Foliar application of microbial consortium formulations suppresses Phomopsis leaf blight, promotes vegetative growth, and modulates biochemical defence in strawberry (Fragaria × ananassa Duch. cv. Camarosa) under protected cultivation
BibTeX
@article{huang2026eosinophils,
title = {{Eosinophils drive intestinal remodelling and innate defence in reproduction}},
author = {Chenyan Huang and Amanda Sun and Jojo Reyes and Jessica Ribeiro de Souza and Thomas R. Cafiero and Krist Antunes Fernandes and Fabrício Marcus Silva Oliveira and Yujie Qiao and Pedro Henrique Gazzinelli-Guimarães and Yuri Pritykin and Ai Ing Lim},
journal = {Nature},
year = {2026},
month = may,
doi = {10.1038/s41586-026-10531-6},
url = {https://doi.org/10.1038/s41586-026-10531-6},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Eosinophils drive intestinal remodelling and innate defence in reproduction
AU - Chenyan Huang
AU - Amanda Sun
AU - Jojo Reyes
AU - Jessica Ribeiro de Souza
AU - Thomas R. Cafiero
AU - Krist Antunes Fernandes
AU - Fabrício Marcus Silva Oliveira
AU - Yujie Qiao
AU - Pedro Henrique Gazzinelli-Guimarães
AU - Yuri Pritykin
AU - Ai Ing Lim
PY - 2026
DA - 2026/05/13
JO - Nature
DO - 10.1038/s41586-026-10531-6
UR - https://doi.org/10.1038/s41586-026-10531-6
AB - 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. From pregnancy until lactation, eosinophils accumulate in the small intestine where they regulate goblet cell fate and enhance innate defences against enteric pathogens.
SN - 0028-0836
SN - 1476-4687
ER -