ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
This article is part of the Research TopicImmunometabolism in Immunological Tolerance and Regulation: Novel Mechanisms and Clinical InterventionsView all 13 articles
Dysfunctional Decidual CD2+CD4+T Cells Regulated by Rev-erbα - GFPT1 - GPI Anchored CD58 Axis of Decidual Stromal Cells Underlies Sleep Disturbance Induced Recurrent Pregnancy Loss
Provisionally accepted
- 1Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
- 2Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
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Background The multifactorial nature of recurrent pregnancy loss (RPL) requires a comprehensive understanding of its diverse risk factors, including sleep disturbance. Previously, we reported decreased Rev-erbα expression in decidual stromal cells from pregnant mice with sleep disturbance (SD) and patients of RPL with sleep disturbance (RS). Methods Omics analyses were used to predict the interaction between Rev-erbα and glutamine-fructose-6-phosphate amidotransferase 1 (GFPT1). Tunicamycin and peptide-N-glycosidase F and phosphatidylinositol-specific phospholipase C treatment were conducted to analyze the glycosylation modification type of CD58. The coculture between decidual immune cells and decidual stroma cells (DSCs) in which Rev-erbα, GFPT1, or CD58 was either knockdown or overexpressed was performed to evaluate the crosstalk of CD58+DSCs and CD2+CD4+T cells. Mouse model with sleep disturbance was established to explore the effect of Rev-erbα - GFPT1 - CD58 - CD2 axis on pregnancy. Results We found that glycometabolism related GFPT1, which regulated by Rev-erbα, increased CD58 expression via glycosylphosphatidylinositol modification not classical Nor O-linked glycosylation modification, leading to the disorder of decidual CD2+CD4+T cells and consequently, resulting in miscarriage. Anti-CD2 antibody significantly decreased the risk of abortion of SD mice, proving a potential therapeutic target for adverse pregnancy outcomes induced by circadian rhythm disruption. Conclusions Rev-erbα - GFPT1 - CD58 - CD2 axis played important role in pregnancy maintenance by regulating the crosstalk between DSCs and decidual CD4+T cells. Given that poor sleep is a common problem during pregnancy, our findings may have important implications for understanding the etiology of RPL and developing targeted therapy of RPL. In addition, we should pay attention to the sleep health of pregnant women, especially those with a history of RPL.
Keywords: CD2, GFPT1, Glycosylphosphatidylinositol, Recurrent pregnancy loss, Sleep disturbance
Received: 12 Sep 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Wang, Qiu, Zhang, Luo, Meng and Cui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Songcun Wang
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