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Maternal group 2 innate lymphoid cells contribute to fetal growth and protection from endotoxin-induced abortion in mice

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Balmas, Elisa 
Rana, Batika MJ 
Hamilton, Russell S 
Shreeve, Norman 
Kieckbusch, Jens 


Group 2 innate lymphoid cells (ILC2s) adapt to tissue physiology and contribute to immunity, inflammatory pathology and metabolism. We show that mouse uterine ILC2s have a heightened type-2 gene signature and expand during pregnancy. Indeed, maternal ILC2s promote fetal growth and protect against fetal mortality upon systemic endotoxin challenge. Absence of ILC2s leads to utero-placental abnormalities, including poor vascular remodelling, increased Il1b and decreased Il4, Il5, and Il13 gene expression, and reduced alternative activation of dendritic cells (DCs) and macrophages. Placentas exhibit signs of adaptation to stress, including larger maternal blood spaces and increased expression of nutrient transporter genes. Endotoxin induces the expansion of IL-1b-producing uterine DCs and, in response, more uterine ILC2s produce IL-4, IL-5 and IL-13. In a protective feedback mechanism, these cytokines suppress IL-1bproducing DCs, in line with a protective role of uILC2s against endotoxin-induced abortion. Uterine ILC2s emerge as pivotal for both normal and complicated pregnancies.



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eLife Sciences Publications Ltd

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Wellcome Trust (200841/Z/16/Z)
We thank the members of the Colucci and McKenzie labs and Tim Halim for suggestions and discussions. This work was funded by the Centre for Trophoblast Research, the Wellcome Trust (Grant 200841/Z/16/Z to FC and 100963/Z/13/Z to ANJM), the Medical Research Council (U105178805 to ANJM) and the Cambridge NIHR BRC Cell Phenotyping Hub to FC. We thank Jan Brosens for providing human endometrial biopsies, Hans-Reimer Rodewald for providing IL7RαCre mice, Esther Perez, Natalia Savinykh and Christian Bowman for cell sorting, the staff at the CBS and ARES animal facilities, particularly Nicola Jeyes and Shona Butler, Helen Jolin and Alexandros Englezakis for help in ARES animal facility, and the Metabolic Research Laboratories (MRL) CBAL, GTU and histology facilities. EB was supported by a CTR PhD fellowship and ANSP by a Royal Society Dorothy Hodgkin Fellowship. The authors declare no competing financial interests. All authors approve the final version of the manuscript.