Enrichment of decidual CD11c + CD8 + T cells with altered immune function in early pregnancy loss

Ling Guo, Anliang Guo, Yaqiu Guo, Shuwen Han, Cameron Klein, Zi-Jiang Chen (), Junhao Yan () and Yan Li ()
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Ling Guo: Shandong University
Anliang Guo: Shandong University
Yaqiu Guo: Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University
Shuwen Han: Shandong University
Cameron Klein: Shandong University
Zi-Jiang Chen: Shandong University
Junhao Yan: Shandong University
Yan Li: Shandong University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Early pregnancy loss (EPL) is closely associated with imbalances in the maternal-foetal immune microenvironment. Here we identify CD11c + CD8 + T cells, an unconventional cytotoxic T cell subset, as significantly enriched and activated in EPL cases. These cells contribute to immune dysregulation and inhibit trophoblast invasion through secreting granzyme B, perforin, CD107a, TNF-α, and IFN-γ. Furthermore, we present an effective early prediction model for EPL, based on cytokine and cytotoxic molecule profiles of CD11c + CD8 + T cells in maternal serum, collected 12-16 days post-embryo transfer. Functional assays reveal that IFN-γ triggers trophoblast pyroptosis via the NLRP3/Caspase-1/GSDMD pathway, impairing trophoblast invasion. In vivo validation using abortion-prone mice and an anti-4-1BB antibody-induced model of CD11c + CD8 + T cell activation confirms increased embryo resorption and reduced trophoblast infiltration. These findings highlight the role of dysregulated CD11c + CD8 + T cells at the maternal-foetal interface in EPL, and suggest their potential as biomarkers and therapeutic targets for EPL-management.

Date: 2025
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DOI: 10.1038/s41467-025-61992-8

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