Single-cell Immune Landscape of Human Recurrent Miscarriage

Area of Science:

• Immunology
• Reproductive Biology
• Genomics

Background:

• Maternal immune tolerance is crucial for successful pregnancy.
• Disruptions in immune tolerance are linked to recurrent miscarriage (RM).
• The decidual and systemic immune environment in RM is not fully understood.

Purpose of the Study:

• To comparatively analyze decidual and peripheral leukocyte cellular and molecular signatures in normal versus unexplained recurrent miscarriage (RM) pregnancies.
• To elucidate the immune pathogenesis underlying early pregnancy loss.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was used to analyze decidual and peripheral leukocytes.
• Integrative analysis identified distinct cell clusters and molecular properties.
• Focus on cellular and molecular signatures in early gestation.

Main Results:

• Significant differences in leukocyte subsets and molecular profiles were observed in RM cases.
• Peripheral cytotoxic T cells, NK cells, and MAIT cells showed enhanced pro-inflammatory status in RM.
• Decidual leukocytes exhibited preferential immune activation, with altered dNK cell subsets, including an increase in a pro-inflammatory CD56+CD16+ dNK subset.

Conclusions:

• This study provides a comprehensive atlas of decidual and peripheral leukocytes in early human pregnancy.
• Altered dNK cell populations and increased immune activation in the decidua are implicated in RM pathogenesis.
• Findings offer critical insights into the immune mechanisms of early pregnancy loss.