2. Academic Validation
  3. Deciphering the Role and Mechanism of Decidual Monocyte-Derived Macrophage Infiltration in Obstetric Antiphospholipid Syndrome at Single-Cell Resolution

Deciphering the Role and Mechanism of Decidual Monocyte-Derived Macrophage Infiltration in Obstetric Antiphospholipid Syndrome at Single-Cell Resolution

  • Adv Sci (Weinh). 2025 Aug 7:e03480. doi: 10.1002/advs.202503480.
Rui Gao 1 2,  Pingying Qing 3,  Hanxiao Chen 2 4,  Zhengyan Hu 1 2,  Qiaoran Yang 5,  Chenyang Lu 6,  Huimin Liu 1 2,  Rujun Zeng 1 2,  Yuanting Tang 2 7,  Fan Yu 2 7,  Jinbiao Han 2 4,  Xin Liao 2 8,  Xun Zeng 1 2,  Lang Qin 1 2 9
Affiliations

Affiliations

  • 1 Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 3 Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 4 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 5 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.
  • 6 Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yet-Sen University, Guangzhou, 510665, China.
  • 7 Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 8 Department of the Central Operating Unit, West China Second University Hospital/West China School of Nursing, Sichuan University, Chengdu, 610041, China.
  • 9 Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
PMID: 40776470 DOI: 10.1002/advs.202503480
Abstract

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder characterized by pathologic pregnancies and the presence of antiphospholipid antibodies (aPLs). Despite significant infiltration of decidual macrophages observed in OAPS patients, the underlying connections between decidual and peripheral immune cells remain unclear. In this study, an integrated single-cell atlas is constructed of the decidua and peripheral blood mononuclear cells (PBMCs) from OAPS patients and HCs. Using this atlas, substantial disparities are identified in immune cells between the decidua and PBMCs. The functional changes in immune cells of OAPS patients are also different in decidua and PBMCs. Moreover, increased infiltration of monocyte-derived macrophages (MDMs) into the decidua is found to contribute to inflammation and trophoblast dysfunction in OAPS. The role of CCL2 is further discovered in recruiting MDMs, driven by excess CCL2 secreted from decidual macrophages stimulated by the aPLs and β2-glycoprotein I complex via the TLR4-NF-κB pathway. Decidual vascular endothelial cells express higher levels of ACKR1, which aggregates CCL2 on their surface. Targeting CCR2 and TLR4 improved pregnancy outcomes in OAPS mouse models induced by aPLs, suggesting that these pathways may serve as potential therapeutic targets for OAPS. This study provides new insights into the pathogenesis of OAPS, particularly regarding decidual MDMs infiltration.

Keywords

antiphospholipid antibody; decidual immune microenvironment; decidual macrophage; obstetric antiphospholipid syndrome; peripheral immune microenvironment.

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