Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome

Yuan Tan; Qi Liu; Zhongxin Li; Shuo Yang; Liyan Cui

doi:10.3389/fimmu.2023.1155222

Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome

Front Immunol. 2023 Mar 31:14:1155222. doi: 10.3389/fimmu.2023.1155222. eCollection 2023.

Authors

Yuan Tan^{1

2

3}, Qi Liu^{1

2

3}, Zhongxin Li^{1

2}, Shuo Yang^{1

2}, Liyan Cui^{1

2}

Affiliations

¹ Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China.
² Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China.
³ Institute of Medical Technology, Peking University Health Science Center, Beijing, China.

Abstract

APS (antiphospholipid syndrome) is a systematic autoimmune disease presenting with the high levels of aPLs (antiphospholipid antibodies). These autoantibodies are involved in various clinical manifestations, mainly including arterial or venous thrombosis formation, proinflammatory response, and recurrent pregnant loss. Pyroptosis is a form of lytic programmed cell death, and it aggravates autoimmune diseases progression via activating NOD-like receptors, especially the NLRP3 inflammasome and its downstream inflammatory factors IL (interleukin)-1β and IL-18. However, the underlying mechanisms of pyroptosis-induced APS progression remain to be elucidated. ECs (endothelial cells), monocytes, platelets, trophoblasts, and neutrophils are prominent participants in APS development. Of significance, pyroptosis of APS-related cells leads to the excessive release of proinflammatory and prothrombotic factors, which are the primary contributors to APOs (adverse pregnancy outcomes), thrombosis formation, and autoimmune dysfunction in APS. Furthermore, pyroptosis-associated medicines have made encouraging advancements in attenuating inflammation and thrombosis. Given the potential of pyroptosis in regulating APS development, this review would systematically expound the molecular mechanisms of pyroptosis, and elaborate the role of pyroptosis-mediated cellular effects in APS progression. Lastly, the prospective therapeutic approaches for APS would be proposed based on the regulation of pyroptosis.

Keywords: APS; cellular effects; mechanisms; pyroptosis; therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Antiphospholipid
Antiphospholipid Syndrome*
Endothelial Cells / metabolism
Female
Humans
Pregnancy
Pyroptosis
Thrombosis* / etiology

Substances

Antibodies, Antiphospholipid

Grants and funding

This work was supported by the National Natural Science Foundation of China (62071011), Key Clinical Specialty Funding Project of Beijing and Hospital-Enterprise Joint Funding Project.