Immune Dysregulation of Decidual NK Cells Mediated by GRIM19 Downregulation Contributes to the Occurrence of Recurrent Pregnancy Loss

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2024 Dec 11

PMID 39663335

Authors

Ying Wang

Anliang Guo

Lin Yang

Xiaojuan Han

Qianni Li

Jin Liu

Yilong Han

Yang Yang

Lan Chao

Affiliations

Soon will be listed here.

Abstract

In patients with recurrent pregnancy loss (RPL), excessive activation of decidual natural killer (dNK) cells has been widely observed, yet the precise underlying mechanisms remain to be elucidated. We collected decidual specimens from RPL patients and controls to assess GRIM19 expression, activation phenotype, cytotoxic function, inflammatory cytokine secretion, and mitochondrial homeostasis in dNK cells. Furthermore, we established a GRIM19-knockout NK-92MI cell line and a GRIM19 ± C57BL/6J mouse model to investigate the relationship between GRIM19 downregulation and dNK immune dysregulation, ultimately contributing to pregnancy loss. Decidual NK cells from RPL patients exhibited significantly lower GRIM19 expression, accompanied by abnormal hyperactivation, enhanced cytotoxicity, and abnormal mitochondrial activation. In vitro experiments confirmed that reduced GRIM19 expression significantly potentiated the cytotoxicity and pro-inflammatory cytokine secretion of NK-92MI cells, while also promoting mitochondrial homeostasis imbalance. Mouse model studies corroborated that GRIM19 downregulation triggers NK cell homeostasis imbalance, contributing to the occurrence of pregnancy loss. Downregulation of GRIM19 in dNK cells contributes to RPL through hyperactivation and disruption of mitochondrial homeostasis, emphasizing its potential as a diagnostic and therapeutic target.

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